Abstract
There is now compelling evidence that the complexity of higher organisms correlates with the relative amount of non-coding RNA rather than the number of protein-coding genes. Previously dismissed as “junk DNA”, it is the non-coding regions of the genome that are responsible for regulation, facilitating complex temporal and spatial gene expression through the combinatorial effect of numerous mechanisms and interactions, working together to fine-tune gene expression. The major regions involved in regulation of a particular gene are the 5′ and 3′ untranslated regions and introns. In addition, pervasive transcription of complex genomes produces a variety of non-coding transcripts that interact with these regions and contribute to gene regulation. This review discusses recent insights into the regulatory roles of the untranslated gene regions and non-coding RNAs in the control of complex gene expression, as well as the implications of this in terms of organism complexity and evolution.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Al-Ahmadi W, Al-Ghamdi M, Al-Haj L, Al-Saif M, Khabar KS (2009) Alternative polyadenylation variants of the RNA binding protein, HuR: abundance, role of AU-rich elements and auto-Regulation. Nucleic Acids Res 37:3612–3624
Amaral PP, Dinger ME, Mercer TR, Mattick JS (2008) The eukaryotic genome as an RNA machine. Science 319:1787–1789
Anastasi G, Cutroneo G, Santoro G, Arco A, Rizzo G, Bramanti P, Rinaldi C, Sidoti A, Amato A, Favaloro A (2008) Costameric proteins in human skeletal muscle during muscular inactivity. J Anat 213:284–295
Andreassi C, Riccio A (2009) To localize or not to localize: mRNA fate is in 3′UTR ends. Trends Cell Biol 19:465–474
Ansari AZ (2009) Riboactivators: transcription activation by noncoding RNA. Crit Rev Biochem Mol Biol 44:50–61
Arce L, Yokoyama NN, Waterman ML (2006) Diversity of LEF/TCF action in development and disease. Oncogene 25:7492–7504
Babbitt CC, Fedrigo O, Pfefferle AD, Boyle AP, Horvath JE, Furey TS, Wray GA (2010) Both noncoding and protein-coding RNAs contribute to gene expression evolution in the primate brain. Genome Biol Evol 2:67–79
Baek D, Davis C, Ewing B, Gordon D, Green P (2007) Characterization and predictive discovery of evolutionarily conserved mammalian alternative promoters. Genome Res 17:145–155
Banerjee AK (1980) 5′-terminal cap structure in eucaryotic messenger ribonucleic acids. Microbiol Rev 44:175–205
Barreau C, Watrin T, Beverley Osborne H, Paillard L (2006) Protein expression is increased by a class III AU-rich element and tethered CUG-BP1. Biochem Biophys Res Commun 347:723–730
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Beaudoin JD, Perreault JP (2010) 5′-UTR G-quadruplex structures acting as translational repressors. Nucleic Acids Res 38:7022–7036
Bellizzi D, Dato S, Cavalcante P, Covello G, di Cianni F, Passarino G, Rose G, de Benedictis G (2007) Characterization of a bidirectional promoter shared between two human genes related to aging: SIRT3 and PSMD13. Genomics 89:143–150
Bharti K, Liu W, Csermely T, Bertuzzi S, Arnheiter H (2008) Alternative promoter use in eye development: the complex role and regulation of the transcription factor MITF. Development 135:1169–1178
Bianchi M, Crinelli R, Giacomini E, Carloni E, Magnani M (2009) A potent enhancer element in the 5′-UTR intron is crucial for transcriptional regulation of the human ubiquitin C gene. Gene 448:88–101
Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE, Kuehn MS, Taylor CM, Neph S, Koch CM, Asthana S, Malhotra A, Adzhubei I, Greenbaum JA, Andrews RM, Flicek P, Boyle PJ, Cao H, Carter NP, Clelland GK, Davis S, Day N, Dhami P, Dillon SC, Dorschner MO, Fiegler H, Giresi PG, Goldy J, Hawrylycz M, Haydock A, Humbert R, James KD, Johnson BE, Johnson EM, Frum TT, Rosenzweig ER, Karnani N, Lee K, Lefebvre GC, Navas PA, Neri F, Parker SC, Sabo PJ, Sandstrom R, Shafer A, Vetrie D, Weaver M, Wilcox S, Yu M, Collins FS, Dekker J, Lieb JD, Tullius TD, Crawford GE, Sunyaev S, Noble WS, Dunham I, Denoeud F, Reymond A, Kapranov P, Rozowsky J, Zheng D, Castelo R, Frankish A, Harrow J, Ghosh S, Sandelin A, Hofacker IL, Baertsch R, Keefe D, Dike S, Cheng J, Hirsch HA, Sekinger EA, Lagarde J, Abril JF, Shahab A, Flamm C, Fried C, Hackermuller J, Hertel J, Lindemeyer M, Missal K, Tanzer A, Washietl S, Korbel J, Emanuelsson O, Pedersen JS, Holroyd N, Taylor R, Swarbreck D, Matthews N, Dickson MC, Thomas DJ, Weirauch MT, Gilbert J et al (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799–816
Blaschke RJ, Topfer C, Marchini A, Steinbeisser H, Janssen JW, Rappold GA (2003) Transcriptional and translational regulation of the Leri-Weill and Turner syndrome homeobox gene SHOX. J Biol Chem 278:47820–47826
Bonnal S, Schaeffer C, Creancier L, Clamens S, Moine H, Prats AC, Vagner S (2003) A single internal ribosome entry site containing a G quartet RNA structure drives fibroblast growth factor 2 gene expression at four alternative translation initiation codons. J biol chem 278:39330–39336
Bostjancic E, Zidar N, Stajer D, Glavac D (2010) MicroRNAs miR-1, miR-133a, miR-133b and miR-208 are dysregulated in human myocardial infarction. Cardiology 115:163–169
Bradnam KR, Korf I (2008) Longer first introns are a general property of eukaryotic gene structure. PLoS One 3:e3093
Burley SK, Roeder RG (1996) Biochemistry and structural biology of transcription factor IID (TFIID). Annu Rev Biochem 65:769–799
Calvo SE, Pagliarini DJ, Mootha VK (2009) Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proc Natl Acad Sci USA 106:7507–7512
Cao Q, Richter JD (2002) Dissolution of the maskin-eIF4E complex by cytoplasmic polyadenylation and poly(A)-binding protein controls cyclin B1 mRNA translation and oocyte maturation. EMBO J 21:3852–3862
Carmell MA, Xuan Z, Zhang MQ, Hannon GJ (2002) The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev 16:2733–2742
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563
Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CA, Taylor MS, Engstrom PG, Frith MC, Forrest AR, Alkema WB, Tan SL, Plessy C, Kodzius R, Ravasi T, Kasukawa T, Fukuda S, Kanamori-Katayama M, Kitazume Y, Kawaji H, Kai C, Nakamura M, Konno H, Nakano K, Mottagui-Tabar S, Arner P, Chesi A, Gustincich S, Persichetti F, Suzuki H, Grimmond SM, Wells CA, Orlando V, Wahlestedt C, Liu ET, Harbers M, Kawai J, Bajic VB, Hume DA, Hayashizaki Y (2006) Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38:626–635
Carter MS, Li S, Wilkinson MF (1996) A splicing-dependent regulatory mechanism that detects translation signals. EMBO J 15:5965–5975
Cenik C, Derti A, Mellor JC, Berriz GF, Roth FP (2010) Genome-wide functional analysis of human 5′ untranslated region introns. Genome Biol 11:R29
Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A, Bozzoni I (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147:358–369
Chamboredon S, Ciais D, Desroches-Castan A, Savi P, Bono F, Feige JJ, Cherradi N (2011) Hypoxia-inducible Factor-1{alpha} mRNA: a new target for destabilization by tristetraprolin in endothelial cells. Mol Biol Cell 22:3366–3378
Chang YF, Imam JS, Wilkinson MF (2007) The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 76:51–74
Chatterjee S, Pal JK (2009) Role of 5′- and 3′-untranslated regions of mRNAs in human diseases. Biol Cell 101:251–262
Chatterjee S, Min L, Karuturi RK, Lufkin T (2010) The role of post-transcriptional RNA processing and plasmid vector sequences on transient transgene expression in zebrafish. Transgenic Res 19:299–304
Chen J, Kastan MB (2010) 5′–3′-UTR interactions regulate p53 mRNA translation and provide a target for modulating p53 induction after DNA damage. Genes Dev 24:2146–2156
Chen CY, Shyu AB (1995) AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci 20:465–470
Chen JM, Ferec C, Cooper DN (2006) A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3′ UTR variants. Hum Genet 120:301–333
Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Bailey DK, Ganesh M, Ghosh S, Bell I, Gerhard DS, Gingeras TR (2005) Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308:1149–1154
Clark MB, Mattick JS (2011) Long noncoding RNAs in cell biology. Semin Cell Dev Biol 22:366–376
Cleynen I, Brants JR, Peeters K, Deckers R, Debiec-Rychter M, Sciot R, van de Ven WJ, Petit MM (2007) HMGA2 regulates transcription of the Imp2 gene via an intronic regulatory element in cooperation with nuclear factor-kappaB. Mol Cancer Res 5:363–372
Cobbold LC, Spriggs KA, Haines SJ, Dobbyn HC, Hayes C, de Moor CH, Lilley KS, Bushell M, Willis AE (2008) Identification of internal ribosome entry segment (IRES)-trans-acting factors for the Myc family of IRESs. Mol Cell Biol 28:40–49
Cooper SJ, Trinklein ND, Anton ED, Nguyen L, Myers RM (2006) Comprehensive analysis of transcriptional promoter structure and function in 1% of the human genome. Genome Res 16:1–10
Cordes KR, Srivastava D (2009) MicroRNA regulation of cardiovascular development. Circ Res 104:724–732
Davuluri RV, Suzuki Y, Sugano S, Plass C, Huang TH (2008) The functional consequences of alternative promoter use in mammalian genomes. Trends Genet 24:167–177
Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. Genes Dev 25:1010–1022
Dejosez M, Levine SS, Frampton GM, Whyte WA, Stratton SA, Barton MC, Gunaratne PH, Young RA, Zwaka TP (2010) Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes Dev 24:1479–1484
Dhami P, Saffrey P, Bruce AW, Dillon SC, Chiang K, Bonhoure N, Koch CM, Bye J, James K, Foad NS, Ellis P, Watkins NA, Ouwehand WH, Langford C, Andrews RM, Dunham I, Vetrie D (2010) Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution. PLoS One 5:e12339
Dickson AM, Wilusz J (2010) Polyadenylation: alternative lifestyles of the A-rich (and famous?). EMBO J 29:1473–1474
Dieci G, Preti M, Montanini B (2009) Eukaryotic snoRNAs: a paradigm for gene expression flexibility. Genomics 94:83–88
Dinger ME, Mercer TR, Mattick JS (2008) RNAs as extracellular signaling molecules. J Mol Endocrinol 40:151–159
Djebali S, Lagarde J, Kapranov P, Lacroix V, Borel C, Mudge JM, Howald C, Foissac S, Ucla C, Chrast J, Ribeca P, Martin D, Murray RR, Yang X, Ghamsari L, Lin C, Bell I, Dumais E, Drenkow J, Tress ML, Gelpi JL, Orozco M, Valencia A, van Berkum NL, Lajoie BR, Vidal M, Stamatoyannopoulos J, Batut P, Dobin A, Harrow J, Hubbard T, Dekker J, Frankish A, Salehi-Ashtiani K, Reymond A, Antonarakis SE, Guigo R, Gingeras TR (2012) Evidence for transcript networks composed of chimeric RNAs in human cells. PLoS One 7:e28213
Djupedal I, Ekwall K (2009) Epigenetics: heterochromatin meets RNAi. Cell Res 19:282–295
Dmitriev SE, Andreev DE, Terenin IM, Olovnikov IA, Prassolov VS, Merrick WC, Shatsky IN (2007) Efficient translation initiation directed by the 900-nucleotide-long and GC-rich 5′ untranslated region of the human retrotransposon LINE-1 mRNA is strictly cap dependent rather than internal ribosome entry site mediated. Mol Cell Biol 27:4685–4697
Dmitriev SE, Andreev DE, Ad’Ianova ZV, Terenin IM, Shatskii IN (2009) Efficient cap-dependent in vitro and in vivo translation of mammalian mRNAs with long and highly structured 5′-untranslated regions. Mol Biol (Mosk) 43:119–125
Duan ZJ, Fang X, Rohde A, Han H, Stamatoyannopoulos G, Li Q (2002) Developmental specificity of recruitment of TBP to the TATA box of the human gamma-globin gene. Proc Natl Acad Sci USA 99:5509–5514
Duffy DL, Montgomery GW, Chen W, Zhao ZZ, Le L, James MR, Hayward NK, Martin NG, Sturm RA (2007) A three-single-nucleotide polymorphism haplotype in intron 1 of OCA2 explains most human eye-color variation. Am J Hum Genet 80:241–252
Eberhardt W, Doller A, Akool El S, Pfeilschifter J (2007) Modulation of mRNA stability as a novel therapeutic approach. Pharmacol Ther 114:56–73
Eberle AB, Stalder L, Mathys H, Orozco RZ, Muhlemann O (2008) Posttranscriptional gene regulation by spatial rearrangement of the 3′ untranslated region. PLoS Biol 6:e92
Eddy J, Maizels N (2008) Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes. Nucleic Acids Res 36:1321–1333
Eisenberg I, Alexander MS, Kunkel LM (2009) miRNAS in normal and diseased skeletal muscle. J Cell Mol Med 13:2–11
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498
Elkon R, Zlotorynski E, Zeller KI, Agami R (2010) Major role for mRNA stability in shaping the kinetics of gene induction. BMC Genomics 11:259
Elton TS, Sansom SE, Martin MM (2010) Trisomy-21 gene dosage over-expression of miRNAs results in the haploinsufficiency of specific target proteins. RNA Biol 7:540–547
Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379
Fablet M, Bueno M, Potrzebowski L, Kaessmann H (2009) Evolutionary origin and functions of retrogene introns. Mol Biol Evol 26:2147–2156
Faghihi MA, Wahlestedt C (2009) Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10:637–643
Fedorova L, Fedorov A (2003) Introns in gene evolution. Genetica 118:123–131
Fejes-Toth K, Sotirova V, Sachidanandam R, Assaf G, Hannon GJ, Kapranov P, Foissac S, Willingham AT, Duttagupta R, Dumais E, Gingeras TR (2009) Post-transcriptional processing generates a diversity of 5’-modified long and short RNAs. Nature 457:1028–1032
Fialcowitz EJ, Brewer BY, Keenan BP, Wilson GM (2005) A hairpin-like structure within an AU-rich mRNA-destabilizing element regulates trans-factor binding selectivity and mRNA decay kinetics. J Biol Chem 280:22406–22417
Fichtlscherer S, de Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Roxe T, Muller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S (2010) Circulating microRNAs in patients with coronary artery disease. Circ Res 107:677–684
Filbin ME, Kieft JS (2009) Toward a structural understanding of IRES RNA function. Curr Opin Struct Biol 19:267–276
Fischer S, Gerriets T, Wessels C, Walberer M, Kostin S, Stolz E, Zheleva K, Hocke A, Hippenstiel S, Preissner KT (2007) Extracellular RNA mediates endothelial-cell permeability via vascular endothelial growth factor. Blood 110:2457–2465
Frenkel-Morgenstern M, Lacroix V, Ezkurdia I, Levin Y, Gabashvili A, Prilusky J, del Pozo A, Tress M, Johnson R, Guigo R, Valencia A (2012) Chimeras taking shape: potential functions of proteins encoded by chimeric RNA transcripts. Genome Res 22:1231–1242
Fritsch C, Herrmann A, Nothnagel M, Szafranski K, Huse K, Schumann F, Schreiber S, Platzer M, Krawczak M, Hampe J, Brosch M (2012) Genome-wide search for novel human uORFs and N-terminal protein extensions using ribosomal footprinting. Genome Res 22:2208–2218
Fu Y, Sun Y, Li Y, Li J, Rao X, Chen C, Xu A (2011) Differential genome-wide profiling of tandem 3′UTRs among human breast cancer and normal cells by high-throughput sequencing. Genome Res 21:741–747
Fukuchi M, Tsuda M (2010) Involvement of the 3′-untranslated region of the brain-derived neurotrophic factor gene in activity-dependent mRNA stabilization. J Neurochem 115:1222–1233
Gallie DR (1991) The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency. Genes Dev 5:2108–2116
Ganapathi M, Srivastava P, Das Sutar SK, Kumar K, Dasgupta D, Pal Singh G, Brahmachari V, Brahmachari SK (2005) Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes. BMC Bioinformatics 6:126
Gerin I, Clerbaux LA, Haumont O, Lanthier N, Das AK, Burant CF, Leclercq IA, Macdougald OA, Bommer GT (2010) Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem 285:33652–33661
Ghosh T, Soni K, Scaria V, Halimani M, Bhattacharjee C, Pillai B (2008) MicroRNA-mediated up-regulation of an alternatively polyadenylated variant of the mouse cytoplasmic {beta}-actin gene. Nucleic Acids Res 36:6318–6332
Gilbert WV (2010) Alternative ways to think about cellular internal ribosome entry. J Biol Chem 285:29033–29038
Gingeras TR (2009) Implications of chimaeric non-co-linear transcripts. Nature 461:206–211
Girard A, Sachidanandam R, Hannon GJ, Carmell MA (2006) A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442:199–202
Gomez D, Guedin A, Mergny JL, Salles B, Riou JF, Teulade-Fichou MP, Calsou P (2010) A G-quadruplex structure within the 5′-UTR of TRF2 mRNA represses translation in human cells. Nucleic Acids Res 38:7187–7198
Goodrich JA, Tjian R (2010) Unexpected roles for core promoter recognition factors in cell-type-specific transcription and gene regulation. Nat Rev Genet 11:549–558
Goodyer CG, Zheng H, Hendy GN (2001a) Alu elements in human growth hormone receptor gene 5′ untranslated region exons. J Mol Endocrinol 27:357–366
Goodyer CG, Zogopoulos G, Schwartzbauer G, Zheng H, Hendy GN, Menon RK (2001b) Organization and evolution of the human growth hormone receptor gene 5′-flanking region. Endocrinology 142:1923–1934
Gorgoni B, Gray NK (2004) The roles of cytoplasmic poly(A)-binding proteins in regulating gene expression: a developmental perspective. Brief Funct Genomic Proteomic 3:125–141
Gorgoni B, Richardson WA, Burgess HM, Anderson RC, Wilkie GS, Gautier P, Martins JP, Brook M, Sheets MD, Gray NK (2011) Poly(A)-binding proteins are functionally distinct and have essential roles during vertebrate development. Proc Natl Acad Sci USA 108:7844–7849
Goss DJ, Kleiman FE (2013) Poly(A) binding proteins: are they all created equal? Wiley interdisciplinary reviews. RNA 4:167–179
Gu S, Jin L, Zhang F, Sarnow P, Kay MA (2009) Biological basis for restriction of microRNA targets to the 3′ untranslated region in mammalian mRNAs. Nat Struct Mol Biol 16:144–150
Guil S, Soler M, Portela A, Carrere J, Fonalleras E, Gomez A, Villanueva A, Esteller M (2012) Intronic RNAs mediate EZH2 regulation of epigenetic targets. Nat Struct Mol Biol 19:664–670
Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076
Hamilton AJ, Baulcombe DC (1999) A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286:950–952
Hawkins PG, Morris KV (2008) RNA and transcriptional modulation of gene expression. Cell Cycle 7:602–607
He Y, Vogelstein B, Velculescu VE, Papadopoulos N, Kinzler KW (2008) The antisense transcriptomes of human cells. Science 322:1855–1857
Holcik M, Lefebvre C, Yeh C, Chow T, Korneluk RG (1999) A new internal-ribosome-entry-site motif potentiates XIAP-mediated cytoprotection. Nat Cell Biol 1:190–192
Huang Y, Shen XJ, Zou Q, Wang SP, Tang SM, Zhang GZ (2011) Biological functions of microRNAs: a review. J Physiol Biochem 67:129–139
Hughes TA (2006) Regulation of gene expression by alternative untranslated regions. Trends Genet 22:119–122
Illingworth RS, Gruenewald-Schneider U, Webb S, Kerr AR, James KD, Turner DJ, Smith C, Harrison DJ, Andrews R, Bird AP (2010) Orphan CpG islands identify numerous conserved promoters in the mammalian genome. PLoS Genet 6:e1001134
Ivanov IP, Loughran G, Atkins JF (2008) uORFs with unusual translational start codons autoregulate expression of eukaryotic ornithine decarboxylase homologs. Proc Natl Acad Sci USA 105:10079–10084
Jackson RJ, Hellen CU, Pestova TV (2010) The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol 11:113–127
Jeffares DC, Penkett CJ, Bahler J (2008) Rapidly regulated genes are intron poor. Trends Genet 24:375–378
Jeffries CD, Fried HM, Perkins DO (2009) Additional layers of gene regulatory complexity from recently discovered microRNA mechanisms. Int J Biochem Cell Biol 42:1236–1242
Ji Z, Tian B (2009) Reprogramming of 3′ untranslated regions of mRNAs by alternative polyadenylation in generation of pluripotent stem cells from different cell types. PLoS One 4:e8419
Ji Z, Lee JY, Pan Z, Jiang B, Tian B (2009) Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development. Proc Natl Acad Sci USA 106:7028–7033
Juven-Gershon T, Hsu JY, Theisen JW, Kadonaga JT (2008) The RNA polymerase II core promoter - the gateway to transcription. Curr Opin Cell Biol 20:253–259
Kandasamy K, Joseph K, Subramaniam K, Raymond JR, Tholanikunnel BG (2005) Translational control of beta2-adrenergic receptor mRNA by T-cell-restricted intracellular antigen-related protein. J Biol Chem 280:1931–1943
Kapp LD, Lorsch JR (2004) The molecular mechanics of eukaryotic translation. Annu Rev Biochem 73:657–704
Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, Denicola G, Webster KA, Weiss D, Perez-Mancera PA, Krauthammer M, Halaban R, Provero P, Adams DJ, Tuveson DA, Pandolfi PP (2011) In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147:382–395
Kedde M, Strasser MJ, Boldajipour B (2007) RNA-binding protein Dnd1 inhibits microRNA access to target mRNA. Cell 131:1273–1286
King MC, Wilson AC (1975) Evolution at two levels in humans and chimpanzees. Science 188:107–116
Klattenhoff C, Theurkauf W (2008) Biogenesis and germline functions of piRNAs. Development 135:3–9
Knapinska AM, Gratacos FM, Krause CD, Hernandez K, Jensen AG, Bradley JJ, Wu X, Pestka S, Brewer G (2011) Chaperone Hsp27 modulates AUF1 proteolysis and AU-rich element-mediated mRNA degradation. Mol Cell Biol 31:1419–1431
Kochetov AV, Ischenko IV, Vorobiev DG, Kel AE, Babenko VN, Kisselev LL, Kolchanov NA (1998) Eukaryotic mRNAs encoding abundant and scarce proteins are statistically dissimilar in many structural features. FEBS Lett 440:351–355
Komar AA, Hatzoglou M (2005) Internal ribosome entry sites in cellular mRNAs: mystery of their existence. J Biol Chem 280:23425–23428
Kozak M (1987) Effects of intercistronic length on the efficiency of reinitiation by eucaryotic ribosomes. Mol Cell Biol 7:3438–3445.
Kozak M (1989) The scanning model for translation: an update. J Cell Biol 108:229–241
Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597–610
Krummheuer J, Johnson AT, Hauber I, Kammler S, Anderson JL, Hauber J, Purcell DF, Schaal H (2007) A minimal uORF within the HIV-1 vpu leader allows efficient translation initiation at the downstream env AUG. Virology 363:261–271
Kuhn U, Gundel M, Knoth A, Kerwitz Y, Rudel S, Wahle E (2009) Poly(A) tail length is controlled by the nuclear poly(A)-binding protein regulating the interaction between poly(A) polymerase and the cleavage and polyadenylation specificity factor. J Biol Chem 284:22803–22814
Kumari S, Bugaut A, Huppert JL, Balasubramanian S (2007) An RNA G-quadruplex in the 5′ UTR of the NRAS proto-oncogene modulates translation. Nat Chem Biol 3:218–221
Kumari S, Bugaut A, Balasubramanian S (2008) Position and stability are determining factors for translation repression by an RNA G-quadruplex-forming sequence within the 5′ UTR of the NRAS proto-oncogene. Biochemistry 47:12664–12669
Lajevic MD, Koduvayur SP, Caffrey V, Cohen RL, Chambers DA (2010) Thy-1 mRNA destabilization by norepinephrine a 3′ UTR cAMP responsive decay element and involves RNA binding proteins. Brain Behav Immun 24:1078–1088
Lee I, Ajay SS, Yook JI, Kim HS, Hong SH, Kim NH, Dhanasekaran SM, Chinnaiyan AM, Athey BD (2009) New class of microRNA targets containing simultaneous 5′-UTR and 3′-UTR interaction sites. Genome Res 19:1175–1183
Lee JE, Lee JY, Wilusz J, Tian B, Wilusz CJ (2010) Systematic analysis of cis-elements in unstable mRNAs demonstrates that CUGBP1 is a key regulator of mRNA decay in muscle cells. PLoS One 5:e11201
Levine M, Tjian R (2003) Transcription regulation and animal diversity. Nature 424:147–151
Lifton RP, Goldberg ML, Karp RW, Hogness DS (1978) The organization of the histone genes in Drosophila melanogaster: functional and evolutionary implications. Cold Spring Harb Symp Quant Biol 42(Pt 2):1047–1051
Lin H (2007) piRNAs in the germ line. Science 316:397
Lin JM, Collins PJ, Trinklein ND, Fu Y, Xi H, Myers RM, Weng Z (2007) Transcription factor binding and modified histones in human bidirectional promoters. Genome Res 17:818–827
Liu L, Dilworth D, Gao L, Monzon J, Summers A, Lassam N, Hogg D (1999) Mutation of the CDKN2A 5′ UTR creates an aberrant initiation codon and predisposes to melanoma. Nat Genet 21:128–132
Lopez De Silanes I, Quesada MP, Esteller M (2007) Aberrant regulation of messenger RNA 3′-untranslated region in human cancer. Cell Oncol 29:1–17
Louro R, Smirnova AS, Verjovski-Almeida S (2009) Long intronic noncoding RNA transcription: expression noise or expression choice? Genomics 93:291–298
Lukavsky PJ (2009) Structure and function of HCV IRES domains. Virus Res 139:166–171
Lyabin DN, Eliseeva IA, Skabkina OV, Ovchinnikov LP (2011) Interplay between Y-box-binding protein 1 (YB-1) and poly(A) binding protein (PABP) in specific regulation of YB-1 mRNA translation. RNA Biol 8:883–892
Macdonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, Barnes G, Taylor SA, James M, Groot N, Macfarlane H, Jenkins B, Anderson MA, Wexler NS, Gusella JF, Bates GP, Baxendale S, Hummerich H, Kirby S, North M, Youngman S, Mott R, Zehetner G, Sedlacek Z, Poustka A, Frischauf A-M, Lehrach H, Buckler AJ, Church D, Doucette-Stamm L, O’Donovan MC, Riba-Ramirez L, Shah M, Stanton VP, Strobel SA, Draths KM, Wales JL, Dervan P, Housman DE, Altherr M, Shiang R, Thompson L, Fielder T, Wasmuth JJ, Tagle D, Valdes J, Elmer L, Allard M, Castilla L, Swaroop M, Blanchard K, Collins FS, Snell R, Holloway T, Gillespie K, Datson N, Shaw D, Harper PS (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983
Mangus DA, Evans MC, Jacobson A (2003) Poly(A)-binding proteins: multifunctional scaffolds for the post-transcriptional control of gene expression. Genome Biol 4:223
Mantovani R (1998) A survey of 178 NF-Y binding CCAAT boxes. Nucleic Acids Res 26:1135–1143
Martinez E, Chiang CM, GE H, Roeder RG (1994) TATA-binding protein-associated factor(s) in TFIID function through the initiator to direct basal transcription from a TATA-less class II promoter. EMBO J 13:3115–3126.
Martinez E, Zhou Q, L'etoile ND, Oelgeschlager T, Berk AJ, Roeder RG (1995) Core promoter-specific function of a mutant transcription factor TFIID defective in TATA-box binding. Proc Natl Acad Sci USA 92:11864–11868.
Maston GA, Evans SK, Green MR (2006) Transcriptional regulatory elements in the human genome. Annu Rev Genomics Hum Genet 7:29–59
Mathers JC, Strathdee G, Relton CL (2010) Induction of epigenetic alterations by dietary and other environmental factors. Adv Genet 71:3–39
Mattick JS (1994) Introns: evolution and function. Curr Opin Genet Dev 4:823–831
Mattick JS (2001) Non-coding RNAs: the architects of eukaryotic complexity. EMBO Rep 2:986–991
Mattick JS (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. Bioessays 25:930–939
Mattick JS (2004) RNA regulation: a new genetics? Nat Rev Genet 5:316–323
Mattick JS (2011a) The central role of RNA in human development and cognition. FEBS Lett 585:1600–1616
Mattick JS (2011b) The central role of RNA in the genetic programming of complex organisms. An Acad Bras Cienc 82:933–939
Mattick JS, Makunin IV (2005) Small regulatory RNAs in mammals. Hum Mol Genet 14(Spec No 1):R121–R132
Mattick JS, Mehler MF (2008) RNA editing, DNA recoding and the evolution of human cognition. Trends Neurosci 31:227–233
Mattick JS, Amaral PP, Dinger ME, Mercer TR, Mehler MF (2009a) RNA regulation of epigenetic processes. Bioessays 31:51–59
Mattick JS, Taft RJ, Faulkner GJ (2009b) A global view of genomic information–moving beyond the gene and the master regulator. Trends Genet 26:21–28
Mayr C, Bartel DP (2009) Widespread shortening of 3′UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell 138:673–684
Mazumder B, Seshadri V, Fox PL (2003) Translational control by the 3′-UTR: the ends specify the means. Trends Biochem Sci 28:91–98
McClelland S, Shrivastava R, Medh JD (2009) Regulation of Translational Efficiency by Disparate 5′UTRs of PPARgamma Splice Variants. PPAR Res 2009:193413
McLean CY, Reno PL, Pollen AA, Bassan AI, Capellini TD, Guenther C, Indjeian VB, Lim X, Menke DB, Schaar BT, Wenger AM, Bejerano G, Kingsley DM (2011) Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature 471:216–219
Mehler MF, Mattick JS (2006) Non-coding RNAs in the nervous system. J Physiol 575:333–341
Meijer HA, Thomas AA (2002) Control of eukaryotic protein synthesis by upstream open reading frames in the 5′-untranslated region of an mRNA. Biochem J 367:1–11
Meisner NC, Hackermuller J, Uhl V, Aszodi A, Jaritz M, Auer M (2004) mRNA openers and closers: modulating AU-rich element-controlled mRNA stability by a molecular switch in mRNA secondary structure. ChemBioChem 5:1432–1447
Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC (2004) Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise. Nat Genet 36:1073–1078
Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10:155–159
Mercer TR, Wilhelm D, Dinger ME, Solda G, Korbie DJ, Glazov EA, Truong V, Schwenke M, Simons C, Matthaei KI, Saint R, Koopman P, Mattick JS (2010) Expression of distinct RNAs from 3′ untranslated regions. Nucleic Acids Res 39:2393–2403
Meyer S, Temme C, Wahle E (2004) Messenger RNA turnover in eukaryotes: pathways and enzymes. Crit Rev Biochem Mol Biol 39:197–216
Mignone F, Gissi C, Liuni S, Pesole G (2002) Untranslated regions of mRNAs. Genome Biol 3:reviews0004
Mitchell SF, Walker SE, Algire MA, Park EH, Hinnebusch AG, Lorsch JR (2010) The 5′-7-methylguanosine cap on eukaryotic mRNAs serves both to stimulate canonical translation initiation and to block an alternative pathway. Mol Cell 39:950–962
Modarresi F, Faghihi MA, Lopez-Toledano MA, Fatemi RP, Magistri M, Brothers SP, van der Brug MP, Wahlestedt C (2012) Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol 30:453–459
Morris KV (2009) RNA-directed transcriptional gene silencing and activation in human cells. Oligonucleotides 19:299–306
Morris DR, Geballe AP (2000) Upstream open reading frames as regulators of mRNA translation. Mol Cell Biol 20:8635–8642
Mortensen RD, Serra M, Steitz JA, Vasudevan S (2011) Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA-protein complexes (microRNPs). Proc Natl Acad Sci USA 108:8281–8286
Munzarova V, Panek J, Gunisova S, Danyi I, Szamecz B, Valasek LS (2011) Translation reinitiation relies on the interaction between eIF3a/TIF32 and progressively folded cis-acting mRNA elements preceding short uORFs. PLoS Genet 7:e1002137
Muro EM, Mah N, Andrade-Navarro MA (2011) Functional evidence of post-transcriptional regulation by pseudogenes. Biochimie 93:1916–1921
Nahkuri S, Taft RJ, Mattick JS (2009) Nucleosomes are preferentially positioned at exons in somatic and sperm cells. Cell Cycle 8:3420–3424
Nakaya HI, Amaral PP, Louro R, Lopes A, Fachel AA, Moreira YB, El-Jundi TA, da Silva AM, Reis EM, Verjovski-Almeida S (2007) Genome mapping and expression analyses of human intronic noncoding RNAs reveal tissue-specific patterns and enrichment in genes related to regulation of transcription. Genome Biol 8:R43
Nolis IK, McKay DJ, Mantouvalou E, Lomvardas S, Merika M, Thanos D (2009) Transcription factors mediate long-range enhancer-promoter interactions. Proc Natl Acad Sci USA 106:20222–20227
O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 104:1604–1609
Okada M, Nakajima K, Yaoita Y (2012) Translational regulation by the 5′-UTR of thyroid hormone receptor alpha mRNA. J Biochem 151:519–531
Okamura K, Lai EC (2008) Endogenous small interfering RNAs in animals. Nat Rev Mol Cell Biol 9:673–678
Ong CT, Corces VG (2011) Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat Rev Genet 12:283–293
Ott CJ, Blackledge NP, Kerschner JL, Leir SH, Crawford GE, Cotton CU, Harris A (2009) Intronic enhancers coordinate epithelial-specific looping of the active CFTR locus. Proc Natl Acad Sci USA 106:19934–19939
Oyama M, Itagaki C, Hata H, Suzuki Y, Izumi T, Natsume T, Isobe T, Sugano S (2004) Analysis of small human proteins reveals the translation of upstream open reading frames of mRNAs. Genome Res 14:2048–2052
Oyama M, Kozuka-Hata H, Suzuki Y, Semba K, Yamamoto T, Sugano S (2007) Diversity of translation start sites may define increased complexity of the human short ORFeome. Mol Cell Proteomics 6:1000–1006
Paik JH, Jang JY, Jeon YK, Kim WY, Kim TM, Heo DS, Kim CW (2011) MicroRNA-146a Downregulates NF{kappa}B Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma. Clin Cancer Res 17:4761–4771
Patikoglou GA, Kim JL, Sun L, Yang SH, Kodadek T, Burley SK (1999) TATA element recognition by the TATA box-binding protein has been conserved throughout evolution. Gene Dev 13:3217–3230.
Paz-Yaacov N, Levanon EY, Nevo E, Kinar Y, Harmelin A, Jacob-Hirsch J, Amariglio N, Eisenberg E, Rechavi G (2010) Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates. Proc Natl Acad Sci USA 107:12174–12179
Peabody DS (1989) Translation initiation at non-AUG triplets in mammalian cells. J Biol Chem 264:5031–5035
Pelham HR, Jackson RJ (1976) An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem 67:247–256
Pesole G, Mignone F, Gissi C, Grillo G, Licciulli F, Liuni S (2001) Structural and functional features of eukaryotic mRNA untranslated regions. Gene 276:73–81
Pickering BM, Willis AE (2005) The implications of structured 5′ untranslated regions on translation and disease. Semin Cell Dev Biol 16:39–47
Pink RC, Wicks K, Caley DP, Punch EK, Jacobs L, Carter DR (2011) Pseudogenes: pseudo-functional or key regulators in health and disease? RNA 17:792–798
Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465:1033–1038
Pollard KS, Salama SR, King B, Kern AD, Dreszer T, Katzman S, Siepel A, Pedersen JS, Bejerano G, Baertsch R, Rosenbloom KR, Kent J, Haussler D (2006) Forces shaping the fastest evolving regions in the human genome. PLoS Genet 2:e168
Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641
Prabhakar S, Visel A, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Morrison H, Fitzpatrick DR, Afzal V, Pennacchio LA, Rubin EM, Noonan JP (2008) Human-specific gain of function in a developmental enhancer. Science 321:1346–1350
Prasanth KV, Spector DL (2007) Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum. Genes Dev 21:11–42
Preker P, Nielsen J, Kammler S, Lykke-Andersen S, Christensen MS, Mapendano CK, Schierup MH, Jensen TH (2008) RNA exosome depletion reveals transcription upstream of active human promoters. Science 322:1851–1854
Preker P, Almvig K, Christensen MS, Valen E, Mapendano CK, Sandelin A, Jensen TH (2011) PROMoter uPstream Transcripts share characteristics with mRNAs and are produced upstream of all three major types of mammalian promoters. Nucleic Acids Res 39:7179–7193
Qureshi IA, Mehler MF (2012) Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease. Nat Rev Neurosci 13:528–541
Rapti A, Trangas T, Samiotaki M, Ioannidis P, Dimitriadis E, Meristoudis C, Veletza S, Courtis N (2010) The structure of the 5′-untranslated region of mammalian poly(A) polymerase-alpha mRNA suggests a mechanism of translational regulation. Mol Cell Biochem 340:91–96
Raveh-Amit H, Maissel A, Poller J, Marom L, Elroy-Stein O, Shapira M, Livneh E (2009) Translational control of protein kinase Ceta by two upstream open reading frames. Mol Cell Biol 29:6140–6148
Resch AM, Ogurtsov AY, Rogozin IB, Shabalina SA, Koonin EV (2009) Evolution of alternative and constitutive regions of mammalian 5′UTRs. BMC Genomics 10:162
Reznik B, Lykke-Andersen J (2010) Regulated and quality-control mRNA turnover pathways in eukaryotes. Biochem Soc Trans 38:1506–1510
Riley A, Jordan LE, Holcik M (2010) Distinct 5′UTRs regulate XIAP expression under normal growth conditions and during cellular stress. Nucleic Acids Res 38:4665–4674
Ringner M, Krogh M (2005) Folding free energies of 5′-UTRs impact post-transcriptional regulation on a genomic scale in yeast. PLoS Comput Biol 1:e72
Rodriguez-Trelles F, Tarrio R, Ayala FJ (2006) Origins and evolution of spliceosomal introns. Annu Rev Genet 40:47–76
Rose AB (2008) Intron-mediated regulation of gene expression. Curr Top Microbiol Immunol 326:277–290
Rotem-Dai N, Oberkovitz G, Abu-Ghanem S, Livneh E (2009) PKCeta confers protection against apoptosis by inhibiting the pro-apoptotic JNK activity in MCF-7 cells. Exp Cell Res 315:2616–2623
Saito T, Saetrom P (2010) MicroRNAs–targeting and target prediction. N Biotechnol 27:243–249
Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011) A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146:353–358
Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB (2008) Proliferating cells express mRNAs with shortened 3′ untranslated regions and fewer microRNA target sites. Science 320:1643–1647
Shah ZH, Toompuu M, Hakkinen T, Rovio AT, van Ravenswaay C, de Leenheer EM, Smith RJ, Cremers FP, Cremers CW, Jacobs HT (2001) Novel coding-region polymorphisms in mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) genes in DFNA4 autosomal dominant deafness families. Hum Mutat 17:433–434
Shatsky IN, Dmitriev SE, Terenin IM, Andreev DE (2010) Cap- and IRES-independent scanning mechanism of translation initiation as an alternative to the concept of cellular IRESs. Mol Cells 30:285–293
Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, Weinstock GM, Wilson RK, Gibbs RA, Kent WJ, Miller W, Haussler D (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15:1034–1050
Smale ST, Kadonaga JT (2003) The RNA polymerase II core promoter. Annu Rev Biochem 72:449–479
Smith L (2008) Post-transcriptional regulation of gene expression by alternative 5′-untranslated regions in carcinogenesis. Biochem Soc Trans 36:708–711
Smith L, Brannan RA, Hanby AM, Shaaban AM, Verghese ET, Peter MB, Pollock S, Satheesha S, Szynkiewicz M, Speirs V, Hughes TA (2010a) Differential regulation of oestrogen receptor beta isoforms by 5′ untranslated regions in cancer. J Cell Mol Med, 14:2172–2184
Smith L, Coleman LJ, Cummings M, Satheesha S, Shaw SO, Speirs V, Hughes TA (2010b) Expression of oestrogen receptor beta isoforms is regulated by transcriptional and post-transcriptional mechanisms. Biochem J 429:283–290
Song B, Wang Y, Kudo K, Gavin EJ, Xi Y, Ju J (2008) miR-192 Regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit. Clin Cancer Res 14:8080–8086
Sotiropoulos A, Goujon L, Simonin G, Kelly PA, Postel-Vinay MC, Finidori J (1993) Evidence for generation of the growth hormone-binding protein through proteolysis of the growth hormone membrane receptor. Endocrinology 132:1863–1865
Southard JN, Barrett BA, Bikbulatova L, Ilkbahar Y, Wu K, Talamantes F (1995) Growth hormone (GH) receptor and GH-binding protein messenger ribonucleic acids with alternative 5′-untranslated regions are differentially expressed in mouse liver and placenta. Endocrinology 136:2913–2921
Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM (2005) Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3′UTR evolution. Cell 123:1133–1146
Stefanovic B, Brenner DA (2003) 5′ stem-loop of collagen alpha 1(I) mRNA inhibits translation in vitro but is required for triple helical collagen synthesis in vivo. Journal Biol Chem 278:927–933
Sturm RA, Duffy DL, Zhao ZZ, Leite FP, Stark MS, Hayward NK, Martin NG, Montgomery GW (2008) A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet 82:424–431
Su WY, Xiong H, Fang JY (2010) Natural antisense transcripts regulate gene expression in an epigenetic manner. Biochem Biophys Res Commun 396:177–181
Subramaniam K, Kandasamy K, Joseph K, Spicer EK, Tholanikunnel BG (2011) The 3′-untranslated region length and AU-rich RNA location modulate RNA-protein interaction and translational control of beta(2)-adrenergic receptor mRNA. Mol Cell Biochem 352:125–141
Suzuki Y, Holmes JB, Cerritelli SM, Sakhuja K, Minczuk M, Holt IJ, Crouch RJ (2010) An upstream open reading frame and the context of the two AUG codons affect the abundance of mitochondrial and nuclear RNase H1. Mol Cell Biol 30:5123–5134
Svitkin YV, Ovchinnikov LP, Dreyfuss G, Sonenberg N (1996) General RNA binding proteins render translation cap dependent. EMBO J 15:7147–7155
Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2009) Non-coding RNAs: regulators of disease. J Pathol 220:126–139
Tan S, Guo J, Huang Q, Chen X, Li-Ling J, Li Q, Ma F (2007) Retained introns increase putative microRNA targets within 3′UTRs of human mRNA. FEBS Lett 581:1081–1086
Tanguay RL, Gallie DR (1996) Translational efficiency is regulated by the length of the 3′ untranslated region. Mol Cell Biol 16:146–156
Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, di Cunto F, Lieberman J, Rigoutsos I, Pandolfi PP (2011) Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147:344–357
Torarinsson E, Sawera M, Havgaard JH, Fredholm M, Gorodkin J (2006) Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. Genome Res 16:885–889
Torarinsson E, Yao Z, Wiklund ED, Bramsen JB, Hansen C, Kjems J, Tommerup N, Ruzzo WL, Gorodkin J (2008) Comparative genomics beyond sequence-based alignments: RNA structures in the ENCODE regions. Genome Res 18:242–251
Touriol C, Bornes S, Bonnal S, Audigier S, Prats H, Prats AC, Vagner S (2003) Generation of protein isoform diversity by alternative initiation of translation at non-AUG codons. Biol Cell 95:169–178
Varki A, Geschwind DH, Eichler EE (2008) Explaining human uniqueness: genome interactions with environment, behaviour and culture. Nat Rev Genet 9:749–763
Vasudevan S, Steitz JA (2007) AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2. Cell 128:1105–1118
Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318:1931–1934
Vickaryous MK, Hall BK (2006) Human cell type diversity, evolution, development, and classification with special reference to cells derived from the neural crest. Biol Rev Camb Philos Soc 81:425–455
Vlasova IA, Tahoe NM, Fan D, Larsson O, Rattenbacher B, Sternjohn JR, Vasdewani J, Karypis G, Reilly CS, Bitterman PB, Bohjanen PR (2008) Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1. Mol Cell 29:263–270
Wahlestedt C (2006) Natural antisense and noncoding RNA transcripts as potential drug targets. Drug Discov Today 11:503–508
Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP, Burge CB (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456:470–476
Wassarman DA, Steitz JA (1992) Interactions of small nuclear RNA’s with precursor messenger RNA during in vitro splicing. Science 257:1918–1925
Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, Chiba H, Kohara Y, Kono T, Nakano T, Surani MA, Sakaki Y, Sasaki H (2008) Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature 453:539–543
Wen Y, Liu Y, Xu Y, Zhao Y, Hua R, Wang K, Sun M, Li Y, Yang S, Zhang XJ, Kruse R, Cichon S, Betz RC, Nothen MM, van Steensel MA, van Geel M, Steijlen PM, Hohl D, Huber M, Dunnill GS, Kennedy C, Messenger A, Munro CS, Terrinoni A, Hovnanian A, Bodemer C, de Prost Y, Paller AS, Irvine AD, Sinclair R, Green J, Shang D, Liu Q, Luo Y, Jiang L, Chen HD, Lo WH, McLean WH, He CD, Zhang X (2009) Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis. Nat Genet 41:228–233
Wethmar K, Smink JJ, Leutz A (2010) Upstream open reading frames: molecular switches in (patho)physiology. Bioessays 32:885–893
Williams AH, Liu N, van Rooij E, Olson EN (2009) MicroRNA control of muscle development and disease. Curr Opin Cell Biol 21:461–469
Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494–1504
Winter J, Kunath M, Roepcke S, Krause S, Schneider R, Schweiger S (2007) Alternative polyadenylation signals and promoters act in concert to control tissue-specific expression of the Opitz Syndrome gene MID1. BMC Mol Biol 8:105
Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, Lander ES, Kellis M (2005) Systematic discovery of regulatory motifs in human promoters and 3′UTRs by comparison of several mammals. Nature 434:338–345
Xu Z, Wei W, Gagneur J, Perocchi F, Clauder-Munster S, Camblong J, Guffanti E, Stutz F, Huber W, Steinmetz LM (2009) Bidirectional promoters generate pervasive transcription in yeast. Nature 457:1033–1037
Yang Z, Kaye DM (2009) Mechanistic insights into the link between a polymorphism of the 3′UTR of the SLC7A1 gene and hypertension. Hum Mutat 30:328–333
Yang C, Bolotin E, Jiang T, Sladek FM, Martinez E (2007) Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. Gene 389:52–65
Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304:594–596
Yokogawa T, Shimada N, Takeuchi N, Benkowski L, Suzuki T, Omori A, Ueda T, Nishikawa K, Spremulli LL, Watanabe K (2000) Characterization and tRNA recognition of mammalian mitochondrial seryl-tRNA synthetase. J Biol Chem 275:19913–19920
Zanotto E, Shah ZH, Jacobs HT (2007) The bidirectional promoter of two genes for the mitochondrial translational apparatus in mouse is regulated by an array of CCAAT boxes interacting with the transcription factor NF-Y. Nucleic Acids Res 35:664–677
Zhang R, Su B (2009) Small but influential: the role of microRNAs on gene regulatory network and 3′UTR evolution. J Genet Genomics 36:1–6
Zhang J, Tsaprailis G, Bowden GT (2008) Nucleolin stabilizes Bcl-X L messenger RNA in response to UVA irradiation. Cancer Res 68:1046–1054
Zhao Y, Srivastava D (2007) A developmental view of microRNA function. Trends Biochem Sci 32:189–197
Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129:303–317
Zheng D, Frankish A, Baertsch R, Kapranov P, Reymond A, Choo SW, Lu Y, Denoeud F, Antonarakis SE, Snyder M, Ruan Y, Wei CL, Gingeras TR, Guigo R, Harrow J, Gerstein MB (2007) Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution. Genome Res 17:839–851
Zhou J, Liao J, Zheng X, Shen H (2012) Chimeric RNAs as potential biomarkers for tumor diagnosis. BMB Rep 45:133–140
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2013 The Author(s)
About this chapter
Cite this chapter
Barrett, L.W., Fletcher, S., Wilton, S.D. (2013). Untranslated Gene Regions and Other Non-coding Elements. In: Untranslated Gene Regions and Other Non-coding Elements. SpringerBriefs in Biochemistry and Molecular Biology. Springer, Basel. https://doi.org/10.1007/978-3-0348-0679-4_1
Download citation
DOI: https://doi.org/10.1007/978-3-0348-0679-4_1
Published:
Publisher Name: Springer, Basel
Print ISBN: 978-3-0348-0678-7
Online ISBN: 978-3-0348-0679-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)