Genomic Regulation of MicroRNA Expression in Disease Development

  • Feng LiuEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1617)


MiroRNAs (miRNAs) are an abundant class of regulators of gene expression. Through base paring with messenger RNAs, miRNAs repress the expression levels of other genes, including those encoding transcription factors. On the other hand, the spatial and temporal patterns of miRNAs transcription are subject to regulation by transcription factors. The inter-regulation between miRNAs and TFs integrates two gene regulatory networks—at transcriptional level and post-transcriptional level to fine-tune the gene expression pattern in the development of multicellular organisms. Aberrant regulation at either of these two levels of gene regulation can lead to developmental disorder and disease.

Key words

MicroRNA Transcription factor Promoter Gene regulatory network 


  1. 1.
    Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42(Database issue):D68–D73CrossRefPubMedGoogle Scholar
  2. 2.
    Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6(5):376–385CrossRefPubMedGoogle Scholar
  3. 3.
    Friedman RC et al (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19(1):92–105CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Chiang HR et al (2010) Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. Genes Dev 24(10):992–1009CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10(12):1957–1966CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Lee Y et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23(20):4051–4060CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pfeffer S et al (2005) Identification of microRNAs of the herpesvirus family. Nat Methods 2(4):269–276CrossRefPubMedGoogle Scholar
  8. 8.
    Smale ST, Kadonaga JT (2003) The RNA polymerase II core promoter. Annu Rev Biochem 72:449–479CrossRefPubMedGoogle Scholar
  9. 9.
    Levine M, Cattoglio C, Tjian R (2014) Looping back to leap forward: transcription enters a new era. Cell 157(1):13–25CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Levine M (2010) Transcriptional enhancers in animal development and evolution. Curr Biol 20(17):R754–R763CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Reinhart BJ et al (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772):901–906CrossRefPubMedGoogle Scholar
  12. 12.
    Johnson SM, Lin SY, Slack FJ (2003) The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. Dev Biol 259(2):364–379CrossRefPubMedGoogle Scholar
  13. 13.
    Kai ZS et al (2013) Multiple cis-elements and trans-acting factors regulate dynamic spatio-temporal transcription of let-7 in Caenorhabditis elegans. Dev Biol 374(1):223–233CrossRefPubMedGoogle Scholar
  14. 14.
    Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610PubMedGoogle Scholar
  15. 15.
    Alon U (2007) Network motifs: theory and experimental approaches. Nat Rev Genet 8(6):450–461CrossRefPubMedGoogle Scholar
  16. 16.
    Hobert O (2006) Architecture of a microRNA-controlled gene regulatory network that diversifies neuronal cell fates. Cold Spring Harb Symp Quant Biol 71:181–188CrossRefPubMedGoogle Scholar
  17. 17.
    Johnston RJ, Hobert O (2003) A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426(6968):845–849CrossRefPubMedGoogle Scholar
  18. 18.
    Hobert O (2004) Common logic of transcription factor and microRNA action. Trends Biochem Sci 29(9):462–468CrossRefPubMedGoogle Scholar
  19. 19.
    Posadas DM, Carthew RW (2014) MicroRNAs and their roles in developmental canalization. Curr Opin Genet Dev 27:1–6CrossRefPubMedGoogle Scholar
  20. 20.
    Li X et al (2009) A microRNA imparts robustness against environmental fluctuation during development. Cell 137(2):273–282CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kennell JA et al (2012) The microRNA miR-8 is a positive regulator of pigmentation and eclosion in Drosophila. Dev Dyn 241(1):161–168CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Im HI, Kenny PJ (2012) MicroRNAs in neuronal function and dysfunction. Trends Neurosci 35(5):325–334CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lujambio A, Lowe SW (2012) The microcosmos of cancer. Nature 482(7385):347–355CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhao Y et al (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 129(2):303–317CrossRefPubMedGoogle Scholar
  25. 25.
    Agarwal V et al (2015) Predicting effective microRNA target sites in mammalian mRNAs. eLife 4:e05005CrossRefPubMedCentralGoogle Scholar
  26. 26.
    Consortium EP (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414):57–74CrossRefGoogle Scholar
  27. 27.
    Rivera CM, Ren B (2013) Mapping human epigenomes. Cell 155(1):39–55CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.National Research Center for Translational Medicine (Shanghai), Rui-Jin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

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