Skip to main content
SpringerLink
Log in

Regulation of pri-miRNA Processing Through Smads

  • Chapter
Regulation of microRNAs

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 700))

Abstract

microRNAs (miRNAs) are small (∼22 nucleotides (nt)), noncoding RNAs that play a critical role in diverse biological functions by modulating mRNA stability and translational control. Numerous miRNA profiling studies have indicated that the levels of miRNAs are tightly controlled during developmental stages and various pathophysiological and physiological conditions. Following transcription, the long primary miRNA transcript undergoes a series of coordinated maturation steps to generate the mature miRNA. Signaling pathways that control miRNA biogenesis and the mechanisms of regulation, however, are not well understood. In this chapter, we will discuss the finding that signal transducers of the Transforming Growth Factor β (TGFβ) signaling pathway, the Smads, play a critical regulatory role in the nuclear processing of miRNAs by the RNase III-type protein Drosha.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Moustakas A, Heldin CH. The regulation of TGFβ signal transduction. Development 2009; 136:3699–3714.

    Article  PubMed  CAS  Google Scholar 

  2. ten Dijke P, Arthur HM. Extracellular control of TGFβ signalling in vascular development and disease. Nature Rev Mol Cell Biol 2007; 8:857–868.

    Article  Google Scholar 

  3. Massague J, Blain SW, Lo RS. TGFβ signaling in growth control, cancer and heritable disorders. Cell 2000; 103:295–309.

    Article  PubMed  CAS  Google Scholar 

  4. Massague J, Gomis RR. The logic of TGFβ signaling. FEBS Lett 2006; 580:2811–2820.

    Article  PubMed  CAS  Google Scholar 

  5. Massague J, Seoane J, Wotton D. Smad transcription factors. Genes Dev 2005; 19:2783–2810.

    Article  PubMed  CAS  Google Scholar 

  6. Zhang Y, Musci T, Derynck R. The tumor suppressor Smad4/DPC4 as a central mediator of Smad function. Curr Biol 1997; 7:270–276.

    Article  PubMed  Google Scholar 

  7. Bardeesy N, Cheng KH, Berger JH et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev 2006; 20:3130–3146.

    Article  PubMed  CAS  Google Scholar 

  8. Giehl K, Imamichi Y, Menke A. Smad4-independent TGF-β signaling in tumor cell migration. Cells Tissues Organs 2007; 185:123–130.

    Article  PubMed  CAS  Google Scholar 

  9. Rodriguez A, Griffiths-Jones S, Ashurst JL et al. Identification of mammalian microRNA host genes and transcription units. Genome Res 2004; 14:1902–1910.

    Article  PubMed  CAS  Google Scholar 

  10. Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. Rna 2004; 10:1957–1966.

    Article  PubMed  CAS  Google Scholar 

  11. Lee Y, Kim M, Han J et al. microRNA genes are transcribed by RNApolymerase II. EMBO J 2004; 23:4051–4060.

    Article  PubMed  CAS  Google Scholar 

  12. Grimson A, Farh KK, Johnston WK et al. micro RNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 2007; 27:91–105.

    Article  PubMed  CAS  Google Scholar 

  13. Lewis BP, Bürge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are micro RNA targets. Cell 2005; 120:15–20.

    Article  PubMed  CAS  Google Scholar 

  14. Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3′ UTR. Proc Natl Acad Sci USA 2007; 104:9667–9672.

    Article  PubMed  CAS  Google Scholar 

  15. Forman JJ, Legesse-Miller A, Coller HA. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci USA 2008; 105:14879–14884.

    Article  PubMed  CAS  Google Scholar 

  16. Selbach M, Schwanhausser B, Thierfelder N et al. Widespread changes in protein synthesis induced by microRNAs. Nature 2008; 455:58–63.

    Article  PubMed  CAS  Google Scholar 

  17. Baek D, Villen J, Shin C et al. The impact of microRNAs on protein output. Nature 2008; 455:64–71.

    Article  PubMed  CAS  Google Scholar 

  18. Huppi K, Volfovsky N, Runfola T et al. The identification of microRNAs in a genomically unstable region of human chromosome 8q24. Mol Cancer Res 2008; 6:212–221.

    Article  PubMed  CAS  Google Scholar 

  19. Huppi K, Volfovsky N, Mackiewicz M et al. microRNAs and genomic instability. Semin Cancer Biol 2007; 17:65–73.

    Article  PubMed  CAS  Google Scholar 

  20. Kumar MS, Erkeland SJ, Pester RE et al. Suppression of nonsmall cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci USA 2008; 105:3903–3908.

    Article  PubMed  CAS  Google Scholar 

  21. Lu J, Getz G, Miska EA et al. microRNA expression profiles classify humancancers. Nature 2005; 435:834–838.

    Article  PubMed  CAS  Google Scholar 

  22. Lee Y, Ahn C, Han J et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003; 425:415–419.

    Article  PubMed  CAS  Google Scholar 

  23. Han J, Lee Y, Yeom KH et al. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 2004; 18:3016–3027.

    Article  PubMed  CAS  Google Scholar 

  24. Han J, Lee Y, Yeom KH et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 2006; 125:887–901.

    Article  PubMed  CAS  Google Scholar 

  25. Morlando M, Ballarino M, Gromak N et al. Primary microRNA transcripts are processed cotranscriptionally. Nat Struct Mol Biol 2008; 15:902–909.

    Article  PubMed  CAS  Google Scholar 

  26. Gregory RI, Yan KP, Amuthan G et al. The Microprocessor complex mediates the genesis of microRNAs. Nature 2004; 432:235–240.

    Article  PubMed  CAS  Google Scholar 

  27. Davis BN, Hilyard AC, Lagna G et al. SMAD proteins control DROSHA-mediated microRNA maturation. Nature 2008; 454:56–61.

    Article  PubMed  CAS  Google Scholar 

  28. Yamagata K, Fujiyama S, Ito S et al. Maturation of microrna is hormonally regulated by a nuclear receptor. Mol Cell 2009; 36:340–347.

    Article  PubMed  CAS  Google Scholar 

  29. Fukuda T, Yamagata K, Fujiyama S et al. DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. Nat Cell Biol 2007; 9:604–611.

    Article  PubMed  CAS  Google Scholar 

  30. Fuller-Pace FV. DExD/Hbox RNAhelicases: multifunctional proteins with important roles intranscriptional regulation. Nucleic Acids Res 2006; 34:4206–4215.

    Article  PubMed  CAS  Google Scholar 

  31. Warner DR, Bhattacherjee V, Yin X et al. Functional interaction between Smad, CREB binding protein and p68 RNA helicase. Biochem Biophys Res Commun 2004; 324:70–76.

    Article  PubMed  CAS  Google Scholar 

  32. Fuentealba LC, Eivers E, Ikeda A et al. Integrating patterning signals: Wnt/GSK3 regulates the duration ofthe BMP/Smadl signal. Cell 2007; 131:980–993.

    Article  PubMed  CAS  Google Scholar 

  33. Kretzschmar M, Doody J, Massagué J. Opposing BMP and EGF signalling pathway converge on the TGFβ family mediator Smadl. Nature 1997; 389:618–622.

    Article  PubMed  CAS  Google Scholar 

  34. Lagna G, Hata A, Hemmati-Brivanlou A et al. Partnership between DPC4 and SMAD proteins in TGF-β signalling pathways. Nature 1996; 383:832–836.

    Article  PubMed  CAS  Google Scholar 

  35. Xu L, Yao X, Chen X et al. Msk is required for nuclear import of TGFβ/BMP-activated Smads. J Cell Biol 2007; 178:981–994.

    Article  PubMed  CAS  Google Scholar 

  36. Yao X, Chen X, Cottonham C et al. Preferential utilization of Imp7/8 in nuclear import of Smads. J Biol Chem 2008; 283:22867–22874.

    Article  PubMed  CAS  Google Scholar 

  37. Qian B, Katsaros D, Lu L et al. High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-βl. Breast Cancer Res Treat 2009; 117:131–140.

    Article  PubMed  CAS  Google Scholar 

  38. Suzuki HI, Yamagata K, Sugimoto K et al. Modulation of microRNA processing by p53. Nature 2009; 460:529–533.

    Article  PubMed  CAS  Google Scholar 

  39. Sato MM, Nashimoto M, Katagiri T et al. Bone morphogenetic protein-2 down-regulates miR-206 expression by blocking its maturation process. Biochem Biophys Res Commun 2009; 383:125–129.

    Article  PubMed  CAS  Google Scholar 

  40. Miller SJ, Suthiphongchai T, Zambetti GP et al. p53 binds selectively to the 5′ untranslated region of cdk4, an RNA elementnecessary and sufficient for transforming growthfactor β-and p53-mediated translational inhibition of cdk4. Mol Cell Biol 2000; 20:8420–8431.

    Article  PubMed  CAS  Google Scholar 

  41. Cassiday LA, Mäher LJ 3rd. Having it both ways: transcription factors that bind DNA and RNA. Nucleic Acids Res 2002; 30:4118–4126.

    Article  PubMed  CAS  Google Scholar 

  42. Fuller-Pace FV, Ali S. The DEAD box RNA helicases p68 (Ddx5) and p72 (Ddxl7): novel transcriptional coregulators. Biochem Soc Trans 2008; 36:609–612.

    Article  PubMed  CAS  Google Scholar 

  43. Clark EL, Coulson A, Dalgliesh C et al. The RNA helicase p68 is a novel androgen receptor coactivator involved in splicing and is overexpressed in prostate cancer. Cancer Res 2008; 68:7938–7946.

    Article  PubMed  CAS  Google Scholar 

  44. Endoh H, Maruyama K, Masuhiro Y et al. Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha. Mol Cell Biol 1999; 19:5363–5372.

    PubMed  CAS  Google Scholar 

  45. Yu B, Bi L, Zheng B et al. The FHA domain proteins DAWDLE in Arabidopsis and SNIP1 in humans act in small RNA biogenesis. Proc Natl Acad Sci USA 2008; 105:10073–10078.

    Article  PubMed  CAS  Google Scholar 

  46. Ozsolak F, Poling LL, Wang Z et al. Chromatin structure analyses identify miRNA promoters. Genes Dev 2008; 22:3172–3183.

    Article  PubMed  CAS  Google Scholar 

  47. Corcoran DL, Pandit KV, Gordon B et al. Features of mammalian micro RNA promoters emerge from polymerase II chromatin immunoprecipitation data. PLoS One 2009; 4:e5279.

    Article  PubMed  Google Scholar 

  48. Kato M, Putta S, Wang M et al. TGF-β activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol 2009; 11:881–889.

    Article  PubMed  CAS  Google Scholar 

  49. Qi HH, Ongusaha PP, Myllyharju J et al. Prolyl 4-hydroxylation regulates Argonaute 2 stability. Nature 2008; 455:421–424.

    Article  PubMed  CAS  Google Scholar 

  50. Diederichs S, Haber DA. Dual role for argonautes in microRNA processing and post-transcriptional regulation of microRNA expression. Cell 2007; 131:1097–1108.

    Article  PubMed  CAS  Google Scholar 

  51. Chen L, Shen YH, Wang X et al. Human prolyl-4-hydroxylase alpha(I) transcription is mediated by upstream stimulatory factors. J Biol Chem 2006; 281:10849–10855.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. 800 Washington Street, Box 8486, Boston, MA, 02111, USA

    Akiko Hata

Authors
  1. Akiko Hata
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brandi N. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

    Helge Großhans

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Landes Bioscience and Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hata, A., Davis, B.N. (2010). Regulation of pri-miRNA Processing Through Smads. In: Großhans, H. (eds) Regulation of microRNAs. Advances in Experimental Medicine and Biology, vol 700. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7823-3_2

Download citation

Publish with us

Policies and ethics

Search

Navigation