Abstract
Long non-coding RNAs (lncRNAs), which represent a new frontier in molecular biology, play important roles in regulating gene expression at epigenetic, transcriptional and post-transcriptional levels. More and more lncRNAs have been found to play important roles in normal cell physiological activities, and participate in the development of varieties of tumors and other diseases. Previously, we have only been able to determine the function of lncRNAs through multiple mechanisms, including genetic imprinting, chromatin remodeling, splicing regulation, mRNA decay, and translational regulation. Application of technological advances to research into the function of lncRNAs is extremely important. The major tools for exploring lncRNAs include microarrays, RNA sequencing (RNA-seq), Northern blotting, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), RNA interference (RNAi), RNA-binding protein immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP), crosslinking-immunopurification (CLIP), and bioinformatic prediction. In this review, we highlight the functions of lncRNAs, and advanced methods to research lncRNA-protein interactions.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Spizzo R, Almeida M I, Colombatti A, et al. Long non-coding RNAs and cancer: A new frontier of translational research? Oncogene, 2012, 31: 4577–4587
Carninci P, Hayashizaki Y. Noncoding RNA transcription beyond annotated genes. Curr Opin Genet Dev, 2007, 17: 139–144
Birney E, Stamatoyannopoulos J A, Dutta A, et al. Identification and analysis of functional elements in 1% of the human genome by the encode pilot project. Nature, 2007, 447: 799–816
Kapranov P, Cheng J, Dike S, et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science, 2007, 316: 1484–1488
Carninci P, Kasukawa T, Katayama S, et al. The transcriptional landscape of the mammalian genome. Science, 2005, 309: 1559–1563
Tian D, Sun S, Lee J T. The long non-coding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell, 2010, 143: 390–403
Ørom U A, Derrien T, Beringer M, et al. Long noncoding RNAs with enhancer-like function in human cells. Cell, 2010, 143: 46–58
Hung T, Wang Y, Lin M F, et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet, 2011, 43: 621–629
Huarte M, Guttman M, Feldser D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 142: 409–419
Guttman M, Amit I, Garber M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding rnas in mammals. Nature, 2009, 458: 223–227
Panzitt K, Tschernatsch M M, Guelly C, et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology, 2007, 132: 330–342
Luo J H, Ren B, Keryanov S, et al. Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas. Hepatology, 2006, 44: 1012–1024
Lin R, Maeda S, Liu C, et al. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene, 2007, 26: 851–858
Gupta R A, Shah N, Wang K C, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 2010, 464: 1071–1076
Wang J, Liu X, Wu H, et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res, 2010, 38: 5366–5383
Mourtada-Maarabouni M, Pickard M R, Hedge V L, et al. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene, 2009, 28: 195–208
Zhao J, Dahle D, Zhou Y, et al. Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab, 2005, 90: 2179–2186
Zhang X, Rice K, Wang Y, et al. Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: Isoform structure, expression, and functions. Endocrinology, 2010, 151: 939–947
Zhou Y, Zhong Y, Wang Y, et al. Activation of p53 by MEG3 non-coding RNA. J Biol Chem, 2007, 282: 24731–24742
Pasmant E, Laurendeau I, Heron D, et al. Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: Identification of anril, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res, 2007, 67: 3963–3969
McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science, 2007, 316: 1488–1491
Johnson R. Long non-coding RNAs in huntington’s disease neurodegeneration. Neurobiol Dis, 2012, 46: 245–254
Brosnan C A, Voinnet O. The long and the short of noncoding RNAs. Curr Opin Cell Biol, 2009, 21: 416–425
Erdmann V A, Szymanski M, Hochberg A, et al. Non-coding, mRNA-like RNAs database Y2K. Nucleic Acids Res, 2000, 28: 197–200
Dinger M E, Pang K C, Mercer T R, et al. Nred: A database of long noncoding RNA expression. Nucleic Acids Res, 2009, 37: D122–126
Mituyama T, Yamada K, Hattori E, et al. The functional RNA database 3.0: Databases to support mining and annotation of functional RNAs. Nucleic Acids Res, 2009, 37: D89–92
Amaral P P, Clark M B, Gascoigne D K, et al. lncRNAdb: A reference database for long noncoding RNAs. Nucleic Acids Res, 2011, 39: D146–151
Liao Q, Xiao H, Bu D, et al. NcFANs: A web server for functional annotation of long non-coding RNAs. Nucleic Acids Res, 2011, 39: W118–124
Bu D, Yu K, Sun S, et al. Noncode v3.0: Integrative annotation of long noncoding RNAs. Nucleic Acids Res, 2012, 40: D210–215
Pang K C, Stephen S, Engstrom P G, et al. RNAdb—a comprehensive mammalian noncoding RNA database. Nucleic Acids Res, 2005, 33: D125–130
Pang K C, Stephen S, Dinger M E, et al. RNAdb 2.0-an expanded database of mammalian non-coding RNAs. Nucleic Acids Res, 2007, 35: D178–182
Griffiths-Jones S, Bateman A, Marshall M, et al. Rfam: An RNA family database. Nucleic Acids Res, 2003, 31: 439–441
Griffiths-Jones S, Moxon S, Marshall M, et al. Rfam: Annotating non-coding RNAs in complete genomes. Nucleic Acids Res, 2005, 33: D121–124
Burge S W, Daub J, Eberhardt R, et al. Rfam 11.0: 10 years of RNA families. Nucleic Acids Res, 2013, 41: D226–232
Chen G, Wang Z, Wang D, et al. lncRNAdisease: A database for long-non-coding RNA-associated diseases. Nucleic Acids Res, 2013, 41: D983–986
Yang J H, Li J H, Jiang S, et al. ChiPBase: A database for decoding the transcriptional regulation of long non-coding RNA and microRNA genes from chip-seq data. Nucleic Acids Res, 2013, 41: D177–187
Volders P J, Helsens K, Wang X, et al. LNCipedia: A database for annotated human lncRNA transcript sequences and structures. Nucleic Acids Res, 2013, 41: D246–251
Ponting C P, Oliver P L, Reik W. Evolution and functions of long noncoding RNAs. Cell, 2009, 136: 629–641
Okazaki Y, Furuno M, Kasukawa T, et al. Analysis of the mouse transcriptome based on functional annotation of 60770 full-length cDNAs. Nature, 2002, 420: 563–573
Mercer T R, Dinger M E, Mattick J S. Long non-coding RNAs: Insights into functions. Nat Rev Genet, 2009, 10: 155–159
Mercer T R, Dinger M E, Sunkin S M, et al. Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci USA, 2008, 105: 716–721
Dinger M E, Pang K C, Mercer T R, et al. Differentiating proteincoding and noncoding RNA: Challenges and ambiguities. PLoS Comput Biol, 2008, 4: e1000176
Sone M, Hayashi T, Tarui H, et al. The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons. J Cell Sci, 2007, 120: 2498–2506
Toor N, Keating K S, Pyle A M. Structural insights into RNA splicing. Curr Opin Struct Biol, 2009, 19: 260–266
Lanz R B, Razani B, Goldberg A D, et al. Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proc Natl Acad Sci USA, 2002, 99: 16081–16086
Babak T, Blencowe B J, Hughes T R. Considerations in the identification of functional RNA structural elements in genomic alignments. BMC Bioinformatics, 2007, 8: 33
Mathews D H, Sabina J, Zuker M, et al. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol, 1999, 288: 911–940
Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res, 2003, 31: 3406–3415
Sukosd Z, Knudsen B, Kjems J, et al. Ppfold 3.0: Fast RNA secondary structure prediction using phylogeny and auxiliary data. Bioinformatics, 2012, 28: 2691–2692
Puton T, Kozlowski L P, Rother K M, et al. CompaRNA: A server for continuous benchmarking of automated methods for RNA secondary structure prediction. Nucleic Acids Res, 2013, 41: 4307–4323
Cao X, Yeo G, Muotri A R, et al. Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci, 2006, 29: 77–103
Guttman M, Rinn J L. Modular regulatory principles of large non-coding RNAs. Nature, 2012, 482: 339–346
Struhl K. Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nat Struct Mol Biol, 2007, 14: 103–105
Tsai M C, Manor O, Wan Y, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science, 2010, 329: 689–693
Gong C, Maquat L E. lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature, 2011, 470: 284–288
Arney K L. H19 and IGF2—enhancing the confusion? Trends Genet, 2003, 19: 17–23
Lee J T. The X as model for RNA’s niche in epigenomic regulation. Cold Spring Harb Perspect Biol, 2010, 2: a003749
Stavropoulos N, Lu N, Lee J T. A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice. Proc Natl Acad Sci USA, 2001, 98: 10232–10237
Yap K L, Li S, Munoz-Cabello A M, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of ink4a. Mol Cell, 2010, 38: 662–674
Kino T, Hurt D E, Ichijo T, et al. Noncoding RNA GAS5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal, 2010, 3: ra8
Jolly C, Lakhotia S C. Human sat III and Drosophila hsr omega transcripts: A common paradigm for regulation of nuclear RNA processing in stressed cells. Nucleic Acids Res, 2006, 34: 5508–5514
Tripathi V, Ellis J D, Shen Z, et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 2010, 39: 925–938
Faghihi M A, Modarresi F, Khalil A M, et al. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med, 2008, 14: 723–730
Tripathi V, Shen Z, Chakraborty A, et al. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-Myb. PLoS Genet, 2013, 9: e1003368
Xu D, Yang F, Yuan JH, et al. Long noncoding RNAs associated with liver regeneration 1 accelerates hepatocyte proliferation during liver regeneration by activating Wnt/beta-catenin signaling. Hepatology, 2013, 58: 739–751
Yi F, Yang F, Liu X, et al. RNA-seq identified a super-long intergenic transcript functioning in adipogenesis. RNA Biol, 2013, 10: 991–1002
Kretz M, Siprashvili Z, Chu C, et al. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature, 2013, 493: 231–235
Brannan C I, Dees E C, Ingram R S, et al. The product of the H19 gene may function as an RNA. Mol Cell Biol, 1990, 10: 28–36
Brown C J, Ballabio A, Rupert J L, et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature, 1991, 349: 38–44
Lee J T, Davidow L S, Warshawsky D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nat Genet, 1999, 21: 400–404
Ji P, Diederichs S, Wang W, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene, 2003, 22: 8031–8041
Zhang X, Zhou Y, Mehta K R, et al. A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. J Clin Endocrinol Metab, 2003, 88: 5119–5126
Scaruffi P, Stigliani S, Moretti S, et al. Transcribed-ultra conserved region expression is associated with outcome in high-risk neuroblastoma. BMC Cancer, 2009, 9: 441
Carrieri C, Cimatti L, Biagioli M, et al. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature, 2012, 491: 454–457
Johnsson P, Ackley A, Vidarsdottir L, et al. A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nat Struct Mol Biol, 2013, 20: 440–446
Yoon J H, Abdelmohsen K, Srikantan S, et al. lincRNA-p21 suppresses target mRNA translation. Mol Cell, 2012, 47: 648–655
Pennisi E. Genomics encode project writes eulogy for junk DNA. Science, 2012, 337: 1159, 1161
Shen K, Arslan S, Akopian D, et al. Activated GTPase movement on an RNA scaffold drives co-translational protein targeting. Nature, 2012, 492: 271–275
Grote P, Wittler L, Hendrix D, et al. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell, 2013, 24: 206–214
Klattenhoff C A, Scheuermann J C, Surface L E, et al. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell, 2013, 152: 570–583
Sun L, Goff L A, Trapnell C, et al. Long noncoding RNAs regulate adipogenesis. Proc Natl Acad Sci USA, 2013, 110: 3387–3392
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature, 2013, 495: 333–338
Kung J T, Lee J T. RNA in the loop. Dev Cell, 2013, 24: 565–567
Yang L, Lin C, Jin C, et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature, 2013, 500: 598–602
Gibb E A, Brown C J, Lam W L. The functional role of long non-coding RNA in human carcinomas. Mol Cancer, 2011, 10: 38
Kelley R L, Kuroda M I. Noncoding RNA genes in dosage compensation and imprinting. Cell, 2000, 103: 9–12
Monk D. Deciphering the cancer imprintome. Brief Funct Genomics, 2010, 9: 329–339
Lim D H, Maher E R. Genomic imprinting syndromes and cancer. Adv Genet, 2010, 70: 145–175
Bartolomei M S, Zemel S, Tilghman S M. Parental imprinting of the mouse H19 gene. Nature, 1991, 351: 153–155
Gabory A, Jammes H, Dandolo L. The H19 locus: Role of an imprinted non-coding RNA in growth and development. Bioessays, 2010, 32: 473–480
Hark A T, Schoenherr C J, Katz D J, et al. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/IGF2 locus. Nature, 2000, 405: 486–489
Schoenherr C J, Levorse J M, Tilghman S M. CTCF maintains differential methylation at the IGF2/H19 locus. Nat Genet, 2003, 33: 66–69
Zhao J, Sun B K, Erwin J A, et al. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science, 2008, 322: 750–756
Wutz A, Rasmussen T P, Jaenisch R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet, 2002, 30: 167–174
Saxena A, Carninci P. Long non-coding RNA modifies chromatin: Epigenetic silencing by long non-coding RNAs. Bioessays, 2011, 33: 830–839
Pandey R R, Mondal T, Mohammad F, et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell, 2008, 32: 232–246
Rinn J L, Kertesz M, Wang J K, et al. Functional demarcation of active and silent chromatin domains in human hox loci by noncoding RNAs. Cell, 2007, 129: 1311–1323
Khalil A M, Guttman M, Huarte M, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA, 2009, 106: 11667–11672
Nagano T, Mitchell J A, Sanz L A, et al. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science, 2008, 322: 1717–1720
Umlauf D, Goto Y, Cao R, et al. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of polycomb group complexes. Nat Genet, 2004, 36: 1296–1300
Kaneko S, Li G, Son J, et al. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev, 2010, 24: 2615–2620
Terranova R, Yokobayashi S, Stadler M B, et al. Polycomb group proteins EZH2 and RNF2 direct genomic contraction and imprinted repression in early mouse embryos. Dev Cell, 2008, 15: 668–679
Sleutels F, Zwart R, Barlow D P. The non-coding air RNA is required for silencing autosomal imprinted genes. Nature, 2002, 415: 810–813
Shin J Y, Fitzpatrick G V, Higgins M J. Two distinct mechanisms of silencing by the KvDMR1 imprinting control region. EMBO J, 2008, 27: 168–178
Hayami S, Kelly J D, Cho H S, et al. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer, 2011, 128: 574–586
Schneider C, King R M, Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell, 1988, 54: 787–793
Dinger M E, Amaral P P, Mercer T R, et al. Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res, 2008, 18: 1433–1445
Mortazavi A, Williams B A, McCue K, et al. Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat Methods, 2008, 5: 621–628
Ng S Y, Johnson R, Stanton L W. Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO J, 2012, 31: 522–533
Chisholm K M, Wan Y, Li R, et al. Detection of long non-coding RNA in archival tissue: Correlation with polycomb protein expression in primary and metastatic breast carcinoma. PLoS ONE, 2012, 7: e47998
Tahira A C, Kubrusly M S, Faria M F, et al. Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer. Mol Cancer, 2011, 10: 141
Yang F, Zhang L, Huo X S, et al. Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of Zeste homolog 2 in humans. Hepatology, 2011, 54: 1679–1689
Sui W, Yan Q, Li H, et al. Genome-wide analysis of long noncoding RNA expression in peripheral blood mononuclear cells of uremia patients. J Nephrol, 2012, 26: 731–738
Peiffer J A, Kaushik S, Sakai H, et al. A spatial dissection of the arabidopsis floral transcriptome by MPSS. BMC Plant Biol, 2008, 8: 43
Wang Z, Gerstein M, Snyder M. RNA-seq: A revolutionary tool for transcriptomics. Nat Rev Genet, 2009, 10: 57–63
Lin M, Pedrosa E, Shah A, et al. RNA-seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders. PLoS ONE, 2011, 6: e23356
Huang Q, Lin B, Liu H, et al. RNA-seq analyses generate comprehensive transcriptomic landscape and reveal complex transcript patterns in hepatocellular carcinoma. PLoS ONE, 2011, 6: e26168
Sun K, Chen X, Jiang P, et al. iSeeRNA: Identification of long intergenic non-coding RNA transcripts from transcriptome sequencing data. BMC Genomics, 2013, 14(Suppl 2): S7
Furuno M, Pang K C, Ninomiya N, et al. Clusters of internally primed transcripts reveal novel long noncoding RNAs. PLoS Genet, 2006, 2: e37
Rudkin G T, Stollar B D. High resolution detection of DNA-RNA hybrids in situ by indirect immunofluorescence. Nature, 1977, 265: 472–473
Chureau C, Chantalat S, Romito A, et al. Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region. Hum Mol Genet, 2011, 20: 705–718
Sasaki Y T, Ideue T, Sano M, et al. MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci USA, 2009, 106: 2525–2530
Redrup L, Branco M R, Perdeaux E R, et al. The long noncoding RNA Kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development, 2009, 136: 525–530
Siomi H, Siomi M C. On the road to reading the RNA-interference code. Nature, 2009, 457: 396–404
Brookheart R T, Michel C I, Listenberger L L, et al. The non-coding RNA gadd7 is a regulator of lipid-induced oxidative and endoplasmic reticulum stress. J Biol Chem, 2009, 284: 7446–7454
Chakraborty D, Kappei D, Theis M, et al. Combined RNAi and localization for functionally dissecting long noncoding RNAs. Nat Methods, 2012, 9: 360–362
Petersen M, Wengel J. LNA: A versatile tool for therapeutics and genomics. Trends Biotechnol, 2003, 21: 74–81
Sarma K, Levasseur P, Aristarkhov A, et al. Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA localization to the X chromosome. Proc Natl Acad Sci USA, 2010, 107: 22196–22201
Selth L A, Gilbert C, Svejstrup J Q. RNA immunoprecipitation to determine RNA-protein associations in vivo. Cold Spring Harb Protoc, 2009, 2009: pdb prot5234
Jain R, Devine T, George A D, et al. RIP-chip analysis: RNA-binding protein immunoprecipitation-microarray (Chip) profiling. Methods Mol Biol, 2011, 703: 247–263
Zhao J, Ohsumi T K, Kung J T, et al. Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell, 2010, 40: 939–953
Chu C, Qu K, Zhong F L, et al. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell, 2011, 44: 667–678
Simon M D, Wang C I, Kharchenko P V, et al. The genomic binding sites of a noncoding RNA. Proc Natl Acad Sci USA, 2011, 108: 20497–20502
Fusco D, Bertrand E, Singer R H. Imaging of single mRNAs in the cytoplasm of living cells. Prog Mol Subcell Biol, 2004, 35: 135–150
Raj A, van den Bogaard P, Rifkin S A, et al. Imaging individual mRNA molecules using multiple singly labeled probes. Nat Methods, 2008, 5: 877–879
Rinke J, Appel B, Blocker H, et al. The 5′-terminal sequence of U1 RNA complementary to the consensus 5′ splice site of hnRNA is single-stranded in intact U1 snRNP particles. Nucleic Acids Res, 1984, 12: 4111–4126
Lingner J, Hendrick L L, Cech T R. Telomerase RNAs of different ciliates have a common secondary structure and a permuted template. Genes Dev, 1994, 8: 1984–1998
Wassarman D A, Steitz J A. Structural analyses of the 7SK ribonucleoprotein (RNP), the most abundant human small RNP of unknown function. Mol Cell Biol, 1991, 11: 3432–3445
Jensen K B, Darnell R B. CLIP: Crosslinking and immunoprecipitation of in vivo RNA targets of RNA-binding proteins. Methods Mol Biol, 2008, 488: 85–98
Ule J, Jensen K, Mele A, et al. CLIP: A method for identifying protein-RNA interaction sites in living cells. Methods, 2005, 37: 376–386
Ule J, Jensen K B, Ruggiu M, et al. CLIP identifies Nova-regulated RNA networks in the brain. Science, 2003, 302: 1212–1215
Yeo G W, Coufal N G, Liang T Y, et al. An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells. Nat Struct Mol Biol, 2009, 16: 130–137
Licatalosi D D, Mele A, Fak J J, et al. HITS-CLIP yields genomewide insights into brain alternative RNA processing. Nature, 2008, 456: 464–469
Hafner M, Landthaler M, Burger L, et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell, 2010, 141: 129–141
Konig J, Zarnack K, Rot G, et al. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat Struct Mol Biol, 2010, 17: 909–915
Wolf J J, Dowell R D, Mahony S, et al. Feed-forward regulation of a cell fate determinant by an RNA-binding protein generates asymmetry in yeast. Genetics, 2010, 185: 513–522
Chi S W, Zang J B, Mele A, et al. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature, 2009, 460: 479–486
Yang J H, Li J H, Shao P, et al. Starbase: A database for exploring microRNA-mRNA interaction maps from argonaute CLIP-seq and degradome-seq data. Nucleic Acids Res, 2011, 39: D202–209
Khorshid M, Rodak C, Zavolan M. CLIPZ: A database and analysis environment for experimentally determined binding sites of RNA-binding proteins. Nucleic Acids Res, 2011, 39: D245–252
Liao Q, Liu C, Yuan X, et al. Large-scale prediction of long noncoding RNA functions in a coding-non-coding gene co-expression network. Nucleic Acids Res, 2011, 39: 3864–3878
Bellucci M, Agostini F, Masin M, et al. Predicting protein associations with long noncoding RNAs. Nat Methods, 2011, 8: 444–445
Anders G, Mackowiak S D, Jens M, et al. DoRiNA: A database of RNA interactions in post-transcriptional regulation. Nucleic Acids Res, 2012, 40: D180–186
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at Springerlink.com
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Zhu, J., Fu, H., Wu, Y. et al. Function of lncRNAs and approaches to lncRNA-protein interactions. Sci. China Life Sci. 56, 876–885 (2013). https://doi.org/10.1007/s11427-013-4553-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-013-4553-6