Skip to main content
SpringerLink
Log in
Book cover

Regulation of microRNAs pp 28–35Cite as

Stimulation of pri-miR-18a Processing by hnRNP A1

  • Chapter

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

Abstract

Recent evidence suggests that the canonical miRNA processing pathway can be regulated by a number of positive and negative trans-acting factors. This chapter provides an overview of hnRNP Al-mediated regulation of miR-18a biogenesis. Our laboratory has recently established that the multifunctional RNA-binding protein hnRNP Al is required for the processing of miR-18a at the nuclear step of Drosha-mediated processing. By combining structural and functional analysis of RNA, we showed that hnRNP Al regulates the processing of pri-miR-18a by binding to its terminal loop and reshaping its stem-loop structure, thus allowing for a more effective Drosha cleavage. Furthermore, we linked the event of hnRNP A1-binding to the pri-miR-18a with an unusual phylogenetic sequence conservation of its terminal loop. Bioinformatic and mutational analysis revealed that a number of pri-miRNAs have highly conserved terminal loops, which are predicted to act as landing pads for trans-acting factors influencing miRNA processing. These results underscore a previously uncharacterized role for general RNA-binding proteins as factors that facilitate the processing of specific miRNAs, revealing an additional level of complexity for the regulation of miRNA production and function.

This is a preview of subscription content, 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 2009; 10:126–139.

    Article  PubMed  CAS  Google Scholar 

  2. Denli AM, Tops BB, Plasterk RH et al. Processing of primary micro RNAs by the Microprocessor complex. Nature 2004; 432:231–235.

    Article  PubMed  CAS  Google Scholar 

  3. 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 

  4. 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 

  5. Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol 2004; 14:2162–2167.

    Article  PubMed  CAS  Google Scholar 

  6. Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J 2005; 24:138–148.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Bartel DP. microRNAs: target recognition and regulatory functions. Cell 2009; 136:215–233.

    Article  PubMed  CAS  Google Scholar 

  15. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-trans criptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008; 9:102–114.

    Article  PubMed  CAS  Google Scholar 

  16. Winter J, Jung S, Keller S et al. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 2009; 11:228–234.

    Article  PubMed  CAS  Google Scholar 

  17. Chatterjee S, Grosshans H. Active turnover modulates mature microRNA activity in Caenorhabditis elegans. Nature 2009; 461:546–549.

    Article  PubMed  CAS  Google Scholar 

  18. 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 

  19. Macias S, Michlewski G, Caceres JF. Hormonal regulation of microRNA biogenesis. Mol Cell 2009: 36:172–173.

    Article  PubMed  CAS  Google Scholar 

  20. 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 

  21. 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 

  22. Dreyfuss G, Kim VN, Kataoka N. Messenger-RNA-binding proteins and the messages they carry. Nat Rev Mol Cell Biol 2002; 3:195–205.

    Article  PubMed  CAS  Google Scholar 

  23. Martinez-Contreras R, Cloutier P, Shkreta L et al. hnRNP proteins and splicing control. Adv Exp Med Biol 2007; 623:123–147.

    Article  PubMed  Google Scholar 

  24. Mayeda A, Krainer AR. Regulation of alternative pre-mRNA splicing by hnRNP Al and splicing factor SF2. Cell 1992; 68:365–375.

    Article  PubMed  CAS  Google Scholar 

  25. Mayeda A, Munroe SH, Caceres JF et al. Function of conserved domains of hnRNP Al and other hnRNP A/B proteins. EMBO J 1994; 13:5483–5495.

    PubMed  CAS  Google Scholar 

  26. Caceres JF, Stamm S, Helfman DM et al. Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors. Science 1994; 265: 1706–1709.

    Article  PubMed  CAS  Google Scholar 

  27. Yang X, Bani MR, Lu SJ et al. The Al and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5' splice site selection in vivo. Proc Natl Acad Sci USA 1994; 91:6924–6928.

    Article  PubMed  CAS  Google Scholar 

  28. Martinez-Contreras R, Fisette JF, Nasim FU et al. Intronic Binding Sites for hnRNP A/B and hnRNP F/H Proteins Stimulate Pre-mRNA Splicing. PLoS Biol 2006; 4:e21.

    Article  PubMed  Google Scholar 

  29. Bonnal S, Pileur F, Orsini C et al. Heterogeneous nuclear ribonucleoprotein Al is a novel internal ribosome entry site trans-acting factor that modulates alternative initiation of translation of the fibroblast growth factor 2 mRNA. J Biol Chem 2005; 280:4144–4153.

    Article  PubMed  CAS  Google Scholar 

  30. Cammas A, Pileur F, Bonnal S et al. Cytoplasmic relocalization of heterogeneous nuclear ribonucleoprotein Al controls translation initiation of specific mRNAs. Mol Biol Cell 2007; 18:5048–5059.

    Article  PubMed  CAS  Google Scholar 

  31. Jo OD, Martin J, Bernath A et al. Heterogeneous nuclear ribonucleoprotein Al regulates cyclin D1 and c-myc internal ribosome entry site function through Akt signaling. J Biol Chem 2008; 283:23274–23287.

    Article  PubMed  CAS  Google Scholar 

  32. Ule J, Jensen KB, Ruggiu M et al. CLIP identifies Nova-regulated RNA networks in the brain. Science 2003; 302:1212–1215.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. Guil S, Caceres JF. The multifunctional RNA-binding protein hnRNP Al is required for processing of miR-18a. Nat Struct Mol Biol 2007; 14:591–596.

    Article  PubMed  CAS  Google Scholar 

  35. Tänzer A, Stadler PF. Molecular evolution of a micro RNA cluster. J Mol Biol 2004; 339:327–335.

    Article  PubMed  Google Scholar 

  36. Ota A, Tagawa H, Karnan S et al. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res 2004; 64:3087–3095.

    Article  PubMed  CAS  Google Scholar 

  37. He L, Thomson JM, Hemann MT et al. A micro RNA polycistron as a potential human oncogene. Nature 2005; 435:828–833.

    Article  PubMed  CAS  Google Scholar 

  38. Michlewski G, Guil S, Semple CA et al. Post-transcriptional regulation of miRNAs harboring conserved terminal loops. Mol Cell 2008; 32:383–393.

    Article  PubMed  CAS  Google Scholar 

  39. Kumar A, Wilson SH. Studies of the strand-annealing activity of mammalian hnRNP complex protein Al. Biochemistry 1990; 29:10717–10722.

    Article  PubMed  CAS  Google Scholar 

  40. Pontius BW, Berg P. Renaturation of complementary DNA strands mediated by purified mammalian heterogeneous nuclear ribonucleoprotein Al protein: implications for a mechanism for rapid molecular assembly. Proc Natl Acad Sci USA 1990; 87:8403–8407.

    Article  PubMed  CAS  Google Scholar 

  41. Munroe SH, Dong XF. Heterogeneous nuclear ribonucleoprotein Al catalyzes RNA.RNA annealing. Proc Natl Acad Sci USA 1992; 89:895–899.

    Article  PubMed  CAS  Google Scholar 

  42. Burd CG, Dreyfuss G. RNA binding specificity of hnRNP Al: significance of hnRNP Al high-affinity binding sites in pre-mRNA splicing. EMBO J 1994; 13:1197–1204.

    PubMed  CAS  Google Scholar 

  43. 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 

Download references

Author information

Authors and Affiliations

  1. Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, EH4 2XU, UK

    Javier F. Cáceres

Authors
  1. Gracjan Michlewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sonia Guil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Javier F. Cáceres
    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

Michlewski, G., Guil, S., Cáceres, J.F. (2010). Stimulation of pri-miR-18a Processing by hnRNP A1. 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_3

Download citation

Publish with us

Policies and ethics

Search

Navigation