Skip to main content

An Overview of MicroRNA

  • Chapter
  • 394 Accesses

Abstract

Recently, microRNAs (miRNAs) have emerged as central posttranscriptional regulators of gene expression. miRNAs regulate many key biological processes, including cell growth, death, development and differentiation. This discovery is challenging the central dogma of molecular biology. miRNAs have been known to be involved in development, cell proliferation and apoptosis. Several reports have recently shown that miRNAs might also be involved in filtering out gene expression noise by regulating positive regulatory loops in cells. Loss- or gain-of-function of specific miRNAs appears to be a key event in the genesis of many diverse diseases. Recent studies have shown that miRNAs are important during heart development and adult cardiac physiology, and modulate a diverse spectrum of cardiovascular functions in vivo. miRNAs have been shown to regulate pathways controlled by genes like p53, MYC and RAS, which are closely related to cancer. Single-nucleotide polymorphisms (SNPs) of miRNA binding sites are associated with gene expression levels of the target alleles and cancer. Finally, these miRNA studies also have implications for understanding complex pathways, e.g., interactions between miRNAs, cell signaling and transcription factors, involved in human diseases, and can lead to potential opportunities in manipulating miRNAs as therapeutic targets.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   189.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abelson JF, Kwan KY, O’Roak BJ et al (2005) Sequence variants in SLITRK1 are associated with tourette’s syndrome. Science 310:317–320

    Article  PubMed  CAS  Google Scholar 

  • Abrahante JE, Daul AL, Li M et al (2003) The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Dev Cell 4:625–637

    Article  PubMed  CAS  Google Scholar 

  • Acar M, Becskei A, van Oudenaarden A (2005) Enhancement of cellular memory by reducing stochastic transitions. Nature 435:228–232

    Article  PubMed  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  • Bentwich I, Avniel A, Karov Y et al (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37:766–770

    Article  PubMed  CAS  Google Scholar 

  • Bernstein E, Kim SY, Carmell MA et al (2003) Dicer is essential for mouse development. Nat Genet 35:215–217

    Article  PubMed  CAS  Google Scholar 

  • Blake WJ, Balazsi G, Kohanski MA et al (2006) Phenotypic consequences of promoter-mediated transcriptional noise. Mol Cell 24:853–865

    Article  PubMed  CAS  Google Scholar 

  • Bohnsack MT, Czaplinski K, Gorlich D (2004) Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10:185–191

    Article  PubMed  CAS  Google Scholar 

  • Bracken AP, Ciro M, Cocito A et al (2004) E2F target genes: unraveling the biology. Trends Biochem Sci 29:409–417

    Article  PubMed  CAS  Google Scholar 

  • Brandman O, Ferrell JE Jr, Li R et al (2005) Interlinked fast and slow positive feedback loops drive reliable cell decisions. Science 310:496–498

    Article  PubMed  CAS  Google Scholar 

  • Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  PubMed  CAS  Google Scholar 

  • Calin GA, Liu CG, Sevignani C et al (2004) microRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 101:11755–11760

    Article  PubMed  CAS  Google Scholar 

  • Cao X, Yeo G, Muotri AR et al (2006) Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 29:77–103

    Article  PubMed  CAS  Google Scholar 

  • Care A, Catalucci D, Felicetti F et al (2007) MicroRNA-133 controls cardiac hypertrophy. Nat Med 13:613–618

    Article  PubMed  CAS  Google Scholar 

  • Carthew RW (2006) Gene regulation by microRNAs. Curr Opin Genet Dev 16:203–208

    Article  PubMed  CAS  Google Scholar 

  • Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033

    Article  PubMed  CAS  Google Scholar 

  • Chen K, Rajewsky N (2006) Natural selection on human microRNA binding sites inferred from SNP data. Nat Genet 38:1452–1456

    Article  PubMed  CAS  Google Scholar 

  • Clop A, Marcq F, Takeda H et al (2006) A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nat Genet 38:813–818

    Article  PubMed  CAS  Google Scholar 

  • Costinean S, Zanesi N, Pekarsky Y et al (2006) Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci USA 103:7024–7029

    Article  PubMed  CAS  Google Scholar 

  • Cui Q, Yu Z, Purisima EO, Wang E (2006) Principles of microRNA regulation of a human cellular signaling network. Mol Syst Biol 2:46

    Article  PubMed  Google Scholar 

  • Cui Q, Yu Z, Pan Y et al (2007a) MicroRNAs preferentially target the genes with high transcriptional regulation complexity. Biochem Biophys Res Commun 352:733–738

    Article  PubMed  CAS  Google Scholar 

  • Cui Q, Yu Z, Purisima EO, Wang E (2007b) MicroRNA regulation and interspecific variation of gene expression. Trends Genet 23:372–375

    Article  PubMed  CAS  Google Scholar 

  • Cullen BR (2005) Human immunodeficiency virus: nuclear RNA export unwound. Nature 433:26–27

    Article  PubMed  CAS  Google Scholar 

  • Denli AM, Tops BB, Plasterk RH et al (2004) Processing of primary microRNAs by the microprocessor complex. Nature 432:231–235

    Article  PubMed  CAS  Google Scholar 

  • Fernandez PC, Frank SR, Wang L et al (2003) Genomic targets of the human c-Myc protein. Genes Dev 17:1115–1129

    Article  PubMed  CAS  Google Scholar 

  • Ferrell JE (2002) Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14:140–148

    Article  PubMed  CAS  Google Scholar 

  • Forstemann K, Tomari Y, Du T et al (2005) Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol 3:e236

    Article  PubMed  Google Scholar 

  • Giraldez AJ, Cinalli RM, Glasner ME et al (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science 308:833–838

    Article  PubMed  CAS  Google Scholar 

  • Giraldez AJ, Mishima Y, Rihel J et al (2006) Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312:75–79

    Article  PubMed  CAS  Google Scholar 

  • Golding I, Paulsson J, Zawilski SM et al (2005) Real-time kinetics of gene activity in individual bacteria. Cell 123:1025–1036

    Article  PubMed  CAS  Google Scholar 

  • Gregory RI, Yan KP, Amuthan G et al (2004) The microprocessor complex mediates the genesis of microRNAs. Nature 432:235–240

    Article  PubMed  CAS  Google Scholar 

  • Grishok A, Pasquinelli AE, Conte D et al (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106:23–34

    Article  PubMed  CAS  Google Scholar 

  • Grosshans H, Johnson T, Reinert KL et al (2005) The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans. Dev Cell 8:321–330

    Article  PubMed  CAS  Google Scholar 

  • He L, He X, Lim LP et al (2007) A microRNA component of the p53 tumour suppressor network. Nature 447:1130–1134

    Article  PubMed  CAS  Google Scholar 

  • Hutvagner G, McLachlan J, Pasquinelli AE et al (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293:834–838

    Article  PubMed  CAS  Google Scholar 

  • John B, Enright AJ, Aravin A et al (2004) Human microRNA targets. PLoS Biol 2:e363

    Article  PubMed  Google Scholar 

  • Johnson DG, Cress WD, Jakoi L et al (1994a) Oncogenic capacity of the E2F1 gene. Proc Natl Acad Sci USA 91:12823–12827

    Article  PubMed  CAS  Google Scholar 

  • Johnson DG, Ohtani K, Nevins JR (1994b) Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Genes Dev 8:1514–1525

    Article  PubMed  CAS  Google Scholar 

  • Johnson SM, Grosshans H, Shingara J et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647

    Article  PubMed  CAS  Google Scholar 

  • Ketting RF, Fischer SE, Bernstein E et al (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15:2654–2659

    Article  PubMed  CAS  Google Scholar 

  • Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6:376–385

    Article  PubMed  CAS  Google Scholar 

  • Knight SW, Bass BL (2001) A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 293:2269–2271

    Article  PubMed  CAS  Google Scholar 

  • Krek A, Grun D, Poy MN et al (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500

    Article  PubMed  CAS  Google Scholar 

  • Krutzfeldt J, Stoffel M (2006) MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab 4:9–12

    Article  PubMed  CAS  Google Scholar 

  • Krutzfeldt J, Rajewsky N, Braich R et al (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438:685–689

    Article  PubMed  Google Scholar 

  • Landgraf P, Rusu M, Sheridan R et al (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Leone G, DeGregori J, Sears R et al (1997) Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F. Nature 387:422–426

    Article  PubMed  CAS  Google Scholar 

  • Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Wang F, Lee JA et al (2006) MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila. Genes Dev 20:2793–2805

    Article  PubMed  CAS  Google Scholar 

  • Lim LP, Lau NC, Garrett-Engele P et al (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773

    Article  PubMed  CAS  Google Scholar 

  • Lu J, Getz G, Miska EA et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  PubMed  CAS  Google Scholar 

  • Lund E, Guttinger S, Calado A et al (2004) Nuclear export of microRNA precursors. Science 303:95–98

    Article  PubMed  CAS  Google Scholar 

  • Matsumura I, Tanaka H, Kanakura Y (2003) E2F1 and c-Myc in cell growth and death. Cell Cycle 2:333–338

    PubMed  CAS  Google Scholar 

  • Moss EG, Lee RC, Ambros V (1997) The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88:637–646

    Article  PubMed  CAS  Google Scholar 

  • Pedraza JM, van Oudenaarden A (2005) Noise propagation in gene networks. Science 307:1965–1969

    Article  PubMed  CAS  Google Scholar 

  • Plasterk RH (2006) MicroRNAs in animal development. Cell 124:877–881

    Article  PubMed  CAS  Google Scholar 

  • Raj A, Peskin CS, Tranchina D et al (2006) Stochastic mRNA synthesis in mammalian cells. PLoS Biol 4:e309

    Article  PubMed  Google Scholar 

  • Rajewsky N (2006) microRNA target predictions in animals. Nat Genet 38(Suppl):S8–S13

    Article  PubMed  CAS  Google Scholar 

  • Raver-Shapira N, Marciano E, Meiri E et al (2007) Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell 26:731–743

    Article  PubMed  CAS  Google Scholar 

  • Reinhart BJ, Slack FJ, Basson M et al (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403:901–906

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld N, Young JW, Alon U et al (2005) Gene regulation at the single-cell level. Science 307:1962–1965

    Article  PubMed  CAS  Google Scholar 

  • Shivdasani RA (2006) MicroRNAs: regulators of gene expression and cell differentiation. Blood 108:3646–3653

    Article  PubMed  CAS  Google Scholar 

  • Slack FJ, Basson M, Liu Z et al (2000) The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell 5:659–669

    Article  PubMed  CAS  Google Scholar 

  • Soutschek J, Akinc A, Bramlage B et al (2004) Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432:173–178

    Article  PubMed  CAS  Google Scholar 

  • Valencia-Sanchez MA, Liu J, Hannon GJ et al (2006) Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev 20:515–524

    Article  PubMed  CAS  Google Scholar 

  • van Rooij E, Sutherland LB, Qi X et al (2007) Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 316:575–579

    Article  PubMed  Google Scholar 

  • Voorhoeve PM, le Sage C, Schrier M et al (2006) A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124:1169–1181

    Article  PubMed  CAS  Google Scholar 

  • Wienholds E, Koudijs MJ, van Eeden FJ et al (2003) The microRNA-producing enzyme Dicer1 is essential for zebrafish development. Nat Genet 35:217–218

    Article  PubMed  CAS  Google Scholar 

  • Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75:855–862

    Article  PubMed  CAS  Google Scholar 

  • Yang B, Lin H, Xiao J et al (2007) The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 13:486–491

    Article  PubMed  CAS  Google Scholar 

  • Yi R, Qin Y, Macara IG et al (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17:3011–3016

    Article  PubMed  CAS  Google Scholar 

  • Yu Z, Jian Z, Shen SH et al (2007a) Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos. Nucleic Acids Res 35:152–164

    Article  PubMed  CAS  Google Scholar 

  • Yu Z, Li Z, Jolicoeur N et al (2007b) Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers. Nucleic Acids Res 35:4535–4541

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Ransom JF, Li A et al (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1–2. Cell 129:303–317

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Wang, E. (2008). An Overview of MicroRNA. In: Erdmann, V.A., Poller, W., Barciszewski, J. (eds) RNA Technologies in Cardiovascular Medicine and Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78709-9_1

Download citation

Publish with us

Policies and ethics