Abstract
MicroRNAs (miRNAs), widely distributed, small regulatory RNA genes, target both messenger RNA (mRNA) degradation and suppression of protein translation based on sequence complementarity between the miRNA and its targeted mRNA. Different names have been used to describe various types of miRNA. During evolution, RNA retroviruses or transgenes invaded the eukaryotic genome and inserted itself in the noncoding regions of DNA, conceivably acting as transposon-like jumping genes, providing defense from viral invasion and fine-tuning of gene expression as a secondary level of gene modulation in eukaryotes. When a transposon is inserted in the intron, it becomes an intronic miRNA, taking advantage of the protein synthesis machinery, i.e., mRNA transcription and splicing, as a means for processing and maturation. Recently, miRNAs have been found to play an important, but not life-threatening, role in embryonic development. They might play a pivotal role in diverse biological systems in various organisms, facilitating a quick response and accurate plotting of body physiology and structures. Based on these unique properties, manufactured intronic miRNAs have been developed for in vitro evaluation of gene function, in vivo gene therapy, and generation of transgenic animal models. The biogenesis and identification of miRNAs, potential applications, and future directions for research are presented in this chapter, hopefully providing a guideline for further miRNA and gene function studies.
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
Holley RW (1965) Structure of an alanine transfer ribonucleic acid. JAMA 194:868–871
Maxwell ES, Fournier MJ (1995) The small nucleolar RNAs. Annu Rev Biochem 64:897–934
Tycowski KT, Shu MD, Steitz JA (1996) A mammalian gene with introns instead of exons generating stable RNA products. Nature 379:464–466
Filipowicz W (2000) Imprinted expression of small nucleolar RNAs in brain: time for RNomics. Proc Natl Acad Sci U S A 97:14035–14037
Allmang C, Kufel J, Chanfreau G, Mitchell P, Petfalski E, Tollervey D (1999) Functions of the exosome in rRNA, snoRNA and snRNA synthesis. EMBO J 18:5399–5410
van Hoof A, Parker R (1999) The exosome: a proteasome for RNA? Cell 99:347–350
Frank DN, Roiha H, Guthrie C (1994) Architecture of the U5 small nuclear RNA. Mol Cell Biol 14:2180–2190
Stavianopoulos JG, Karkus JD, Charguff E (1971) Nucleic acid polymerase of the developing chicken embryos: a DNA Polymerase preferring a hybrid template. Proc Natl Acad Sci U S A 68:2207–2211
Stavianopoulos JG, Karkus JD, Charguff E (1972) Mechanism of DNA replication by highly purified DNA polymerase of chicken embryos. Proc Natl Acad Sci USA 69:2609–2613
Wank H, Schroeder R (1996) Antibiotic-induced oligomerisation of group I intron RNA. J Mol Biol 258:53–61
van der Krol AR, Mur LA, Beld M, Mol JN, Stuitje AR (1990) Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression. Plant Cell 2:291–299
Napoli C, Lemieux C, Jorgensen RA (1990) Introduction of a chimeric chalcone synthase gene into Petunia results in reversible co-suppression of homologous genes in trans. Plant Cell 2:279–289
Matzke MA, Primig MJ, Trnovsky J, Matzke AJM (1989) Reversible methylation and inactivation of marker genes in sequentially transformed tobacco plants. EMBO J 8:643–649
Fire A, Xu S, Montgomery MK et al (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811
Shi Y (2003) Mammalian RNAi for the masses. Trends Genet 19:9–12
Sui G, Soohoo C, el Affar B et al (2002) A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc Natl Acad Sci U S A 99:5515–5520
Elbashir SM, Lendeckel W, Tuschl T (2001) RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev 15:188–200
Pasquinelli AE, Reinhart BJ, Slack F et al (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408:86–89
Reinhart BJ, Bartel DP (2002) Small RNAs correspond to centromere heterochromatic repeats. Science 297:1831
Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH (2004) A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 116:779–793
Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854
Lau NC, Lim LP, Weinstein EG, Bartel DP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294:858–862
Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (2003) New microRNAs from mouse and human. RNA 9:175–179
Lee Y, Ahn C, Han J et al (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419
Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U (2003) Nuclear export of microRNA precursors. Science 303:95–98
Ying SY, Lin SL (2005) Intronic microRNAs (miRNAs). Biochem Biophys Res Commun 326:515–520
Lee YS, Nakahara K, Pham JW et al (2004) Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117:69–81
Tang G (2005) siRNA and miRNA: an insight into RISCs. Trends Biochem Sci 30:106–114
Lambowitz AM, Zimmerly S (2004) Mobile group II introns. Annu Rev Genet 38:1–35
Coghlan A, Wolfe KH (2004) Origins of recently gained introns in Caenorhabditis. Proc Natl Acad Sci U S A 101:11362–11367
Harper PS (1989) Myotonic dystrophy, 2nd edn. Saunders, London
Liquori CL, Ricker K, Moseley ML et al (2001) Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 293:864–867
Aravin AA, Sachidanadam R, Girard A, Fejes-Toth K, Hannon GJ (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316:744–747
Siomi MC, Miyoshi T, Siomi H (2010) piRNA-mediated silencing in Drosophila germlines. Semin Cell Dev Biol 21:754–759
Betel D, Sheridan R, Marks DS, Sander C (2007) Computational analysis of mouse piRNA sequence and biogenesis. PLoS Comput Biol 3:2219–2227
Shpiz S, Kwon D, Rozovsky Y, Kalmykova A (2009) rasiRNA pathway controls antisense expression of Drosophila telomeric transposons in the nucleus. Nucleic Acids Res 37:267–278
Pelisson A, Sarot E, Payen-Groschene G, Bucheton A (2007) A novel repeat-associated small interfering RNA -mediated silencing pathway downregulates complementary sense gypsy transcripts in somatic cells of the Drosophila ovary. J Virol 81:1951–1960
Gasciolli V, Mallory AC, Bartel DP, Vaucheret H (2005) Partially redundant functions of Arabidopsis DICER-like enzymes and a role for DCL4 in producing trans-acting siRNAs. Curr Biol 15:1–7
Allen E, Xie Z, Gustafson AM, Carrington JC (2005) MicroRNA-directed phasing during trans-acting siRNA biogenesis in plants. Cell 121:207–221
Li LC, Okino ST, Zhao H, Pookot D, Place RF, Urakami S, Enokida H, Dahiya R (2006) Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A 103:17337–17342
Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A 105:1608–1613
Lin SL, Chang D, Wu DY, Ying SY (2003) A novel RNA splicing-mediated gene silencing mechanism potential for genome evolution. Biochem Biophys Res Commun 310:754–760
Lee Y, Kim M, Han J et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060
Yi R, Qin Y, Macara IG, Cullen BR (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17:3011–3016
Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199–208
Khvorova A, Reynolds A, Jayasena SD (2003) Functional siRNAs and miRNAs exhibit strand bias. Cell 115:209–216
Jones L, Hamilton AJ, Voinnet O, Thomas CL, Maule AJ, Baulcombe DC (1999) RNA-DNA interactions and DNA methylation in post-transcriptional gene silencing. Plant Cell 11:2291–2301
Vaistij FE, Jones L, Baulcombe DC (2002) Spreading of RNA targeting and DNA methylation in RNA silencing requires transcription of the target gene and a putative RNA-dependent RNA polymerase. Plant Cell 14:857–867
Béclin C, Boutet S, Waterhouse P, Vaucheret H (2002) A branched pathway for transgene-induced RNA silencing in plants. Curr Biol 12:684–688
Okamura K, Ishizuka A, Siomi H, Siomi MC (2004) Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. Genes Dev 18:1655–1666
Kidner CA, Martienssen RA (2005) The role of ARGONAUTE1 (AGO1) in meristem formation and identity. Dev Biol 280:504–517
Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R (2005) MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol 7:719–723
Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 15:185–197
Takamizawa J, Konishi H, Yanagisawa K et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756
Karube Y, Tanaka H, Osada H et al (2005) Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci 96:111–115
Xu P, Guo M, Hay BA (2004) MicroRNAs and the regulation of cell death. Trends Genet 20:617–624
Jin P, Alisch RS, Warren ST (2004) RNA and microRNAs in fragile X mental retardation. Nat Cell Biol 6:1048–1053
Gesellchen V, Boutros M (2004) Managing the genome: microRNAs in Drosophila. Differentiation 72:74–80
McManus MT (2003) MicroRNAs and cancer. Semin Cancer Biol 13:253–258
Liu CG, Calin GA, Meloon B et al (2004) An oligonucleotide microchip for genomewide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci U S A 101:9740–9744
Miska EA, Alvarez-Saavedra E, Townsend M et al (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5:R68
Valoczi A, Hornyik C, Varga N, Burgyan J, Kauppinen S, Havelda Z (2004) Sensitive and specific detection of microRNAs by northern blot analysis using LNA-modified oligonucleotide probes. Nucleic Acids Res 32:e175
Giraldez AJ, Cinalli RM, Glasner ME et al (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science 308:833–838
Lai EC, Tomancak P, Williams RW, Rubin GM (2003) Computational identification of Drosophila microRNA genes. Genome Biol 4:R42
Brown JR, Sanseau P (2005) A computational view of microRNAs and their targets. Drug Discov Today 10:595–601
Miyagishi M, Matsumoto S, Taira K (2004) Generation of and shRNAi expression library against the whole human transcripts. Virus Res 102:117–124
Nagl SB (2002) Computational function assignment for potential drug targets: from single genes to cellular systems. Curr Drug Targets 3:387–399
Landthaler M, Yalcin A, Tuschl T (2004) The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol 14:2162–2167
Pardridge WM (2004) Intravenous, non-viral RNAi gene therapy of brain cancer. Expert Opin Biol Ther 4:1103–1113
Zamore PD (2004) Plant RNAi: how a viral silencing suppressor inactivates siRNA. Curr Biol 9:R198–R200
Lecellier CH, Dunoyer P, Arar K et al (2005) A cellular microRNA mediates antiviral defense in human cells. Science 308:557–561
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Ying, SY., Chang, D.C., Lin, SL. (2013). The MicroRNA. In: Ying, SY. (eds) MicroRNA Protocols. Methods in Molecular Biology, vol 936. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-083-0_1
Download citation
DOI: https://doi.org/10.1007/978-1-62703-083-0_1
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-082-3
Online ISBN: 978-1-62703-083-0
eBook Packages: Springer Protocols