Skip to main content

MicroRNAs are single-stranded regulatory RNAs of 18–25 nucleotide length generated from endogenous transcripts that form local hairpin structures. The processing of microRNA transcripts involves the activities of two RNase III enzymes Drosha and Dicer. In this study we analyzed structural features of human microRNA precursors that make these transcripts Drosha and Dicer substrates. The structures of minimal functional primary precursors (pri-microRNAs) and secondary precursors (pre-microRNAs) were predicted. The frequency, nucleotide sequence content and the localization of various structure destabilizing motifs was analyzed. We identified numerous pri-microRNAs which structures strongly depart from the consensus structure and their processing is hard to explain by the existing model of the Microprocessor complex. We also found a biased distribution of symmetric and asymmetric motifs along the pre-microRNA hairpin stem and an over-representation of bulges on its 5′ arm (p < 0.000001), which may have considerable functional implications.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297.

    Article  CAS  PubMed  Google Scholar 

  2. Basyuk, E., Suavet, F., Doglio, A., Bordonne, R., and Bertrand, E. (2003). Human let-7 stem-loop precursors harbor features of RNase III cleavage products. Nucleic Acids Res 31, 6593-6597.

    Article  CAS  PubMed  Google Scholar 

  3. Bernstein, E., Caudy, A. A., Hammond, S. M., and Hannon, G. J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363-366.

    Article  CAS  PubMed  Google Scholar 

  4. Borchert, G. M., Lanier, W., and Davidson, B. L. (2006). RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 13, 1097-1101.

    Article  CAS  PubMed  Google Scholar 

  5. Denli, A. M., Tops, B. B., Plasterk, R. H., Ketting, R. F., and Hannon, G. J. (2004). Processing of primary microRNAs by the microprocessor complex. Nature 432, 231-235.

    Article  CAS  PubMed  Google Scholar 

  6. Gregory, R. I., Chendrimada, T. P., Cooch, N., and Shiekhattar, R. (2005). Human RISC cou-ples microRNA biogenesis and posttranscriptional gene silencing. Cell 123, 631-640.

    Article  CAS  PubMed  Google Scholar 

  7. Gregory, R. I., Yan, K. P., Amuthan, G., Chendrimada, T., Doratotaj, B., Cooch, N., and Shiekhattar, R. (2004). The microprocessor complex mediates the genesis of microRNAs. Nature 432, 235-240.

    Article  CAS  PubMed  Google Scholar 

  8. Griffiths-Jones, S., Grocock, R. J., van Dongen, S., Bateman, A., and Enright, A. J. (2006). miR-Base: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34, D140-144.

    Article  CAS  PubMed  Google Scholar 

  9. Han, J., Lee, Y., Yeom, K. H., Nam, J. W., Heo, I., Rhee, J. K., Sohn, S. Y., Cho, Y., Zhang, B. T., and Kim, V. N. (2006). Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 125, 887-901.

    Article  CAS  PubMed  Google Scholar 

  10. Huang, T. H., Fan, B., Rothschild, M. F., Hu, Z. L., Li, K., and Zhao, S. H. (2007). MiRFinder: an improved approach and software implementation for genome-wide fast microRNA precur-sor scans. BMC Bioinformatics 8, 341.

    Article  PubMed  Google Scholar 

  11. Jiang, P., Wu, H., Wang, W., Ma, W., Sun, X., and Lu, Z. (2007). MiPred: classification of real and pseudo microRNA precursors using random forest prediction model with combined fea-tures. Nucleic Acids Res 35, W339-344.

    Article  PubMed  Google Scholar 

  12. Kim, V. N., and Nam, J. W. (2006). Genomics of microRNA. Trends Genet 22, 165-173.

    Article  CAS  PubMed  Google Scholar 

  13. Krol, J., Sobczak, K., Wilczynska, U., Drath, M., Jasinska, A., Kaczynska, D., and Krzyzosiak, W. J. (2004). Structural features of microRNA (miRNA) precursors and their rel-evance to miRNA biogenesis and small interfering RNA/short hairpin RNA design. J Biol Chem 279, 42230-42239.

    Article  CAS  PubMed  Google Scholar 

  14. Krol, J., Starega-Roslan, J., Milanowska, K., Nowak, D., Kubiaczyk, E., Nowak, M., Majorek, K., Kaminska, K., and Krzyzosiak, W. J. (2006). Structural Features of microRNAs and Their Precursors, In microRNA: Biology, Function & Expression, N. Clarke, and P. Sanseau, eds. (DNA Press), Eagleville, PA, pp. 95-110.

    Google Scholar 

  15. Lai, E. C., Tomancak, P., Williams, R. W., and Rubin, G. M. (2003). Computational identifica-tion of Drosophila microRNA genes. Genome Biol 4, R42.

    Article  PubMed  Google Scholar 

  16. Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A. O., Landthaler, M., et al. (2007). A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401-1414.

    Article  CAS  PubMed  Google Scholar 

  17. Landthaler, M., Yalcin, A., and 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  CAS  PubMed  Google Scholar 

  18. Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Radmark, O., Kim, S., and Kim, V. N. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415-419.

    Article  CAS  PubMed  Google Scholar 

  19. Lee, Y., Kim, M., Han, J., Yeom, K. H., Lee, S., Baek, S. H., and Kim, V. N. (2004). MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23, 4051-4060.

    Article  CAS  PubMed  Google Scholar 

  20. Lewis, B. P., Burge, C. B., and Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20.

    Article  CAS  PubMed  Google Scholar 

  21. Lim, L. P., Glasner, M. E., Yekta, S., Burge, C. B., and Bartel, D. P. (2003). Vertebrate micro-RNA genes. Science 299, 1540.

    Article  CAS  PubMed  Google Scholar 

  22. Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E., and Kutay, U. (2004). Nuclear export of microRNA precursors. Science 303, 95-98.

    Article  CAS  PubMed  Google Scholar 

  23. Macrae, I. J., Zhou, K., and Doudna, J. A. (2007). Structural determinants of RNA recognition and cleavage by Dicer. Nat Struct Mol Biol 14, 934-940.

    Article  CAS  PubMed  Google Scholar 

  24. Macrae, I. J., Zhou, K., Li, F., Repic, A., Brooks, A. N., Cande, W. Z., Adams, P. D., and Doudna, J. A. (2006). Structural basis for double-stranded RNA processing by Dicer. Science 311, 195-198.

    Article  CAS  PubMed  Google Scholar 

  25. Pillai, R. S., Bhattacharyya, S. N., Artus, C. G., Zoller, T., Cougot, N., Basyuk, E., Bertrand, E., and Filipowicz, W. (2005). Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309, 1573-1576.

    Article  CAS  PubMed  Google Scholar 

  26. Provost, P., Dishart, D., Doucet, J., Frendewey, D., Samuelsson, B., and Radmark, O. (2002). Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J 21, 5864-5874.

    Article  CAS  PubMed  Google Scholar 

  27. Ritchie, W., Legendre, M., and Gautheret, D. (2007). RNA stem-loops: to be or not to be cleaved by RNAse III. RNA 13, 457-462.

    Article  CAS  PubMed  Google Scholar 

  28. Saetrom, P., Snove, O., Nedland, M., Grunfeld, T. B., Lin, Y., Bass, M. B., and Canon, J. R. (2006). Conserved microRNA characteristics in mammals. Oligonucleotides 16, 115-144.

    Article  CAS  PubMed  Google Scholar 

  29. Sewer, A., Paul, N., Landgraf, P., Aravin, A., Pfeffer, S., Brownstein, M. J., Tuschl, T., van Nimwegen, E., and Zavolan, M. (2005). Identification of clustered microRNAs using an ab initio prediction method. BMC Bioinformatics 6, 267.

    Article  PubMed  Google Scholar 

  30. Sheng, Y., Engstrom, P. G., and Lenhard, B. (2007). Mammalian MicroRNA prediction through a support vector machine model of sequence and structure. PLoS ONE 2, e946.

    Article  PubMed  Google Scholar 

  31. Wang, X., Zhang, J., Li, F., Gu, J., He, T., Zhang, X., and Li, Y. (2005). MicroRNA identifica-tion based on sequence and structure alignment. Bioinformatics 21, 3610-3614.

    Article  CAS  PubMed  Google Scholar 

  32. Xue, C., Li, F., He, T., Liu, G. P., Li, Y., and Zhang, X. (2005). Classification of real and pseudo microRNA precursors using local structure-sequence features and support vector machine. BMC Bioinformatics 6, 310.

    Article  PubMed  Google Scholar 

  33. Yekta, S., Shih, I. H., and Bartel, D. P. (2004). MicroRNA-directed cleavage of HOXB8 mRNA. Science 304, 594-596.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang, H., Kolb, F. A., Brondani, V., Billy, E., and Filipowicz, W. (2002). Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J 21, 5875-5885.

    Article  CAS  PubMed  Google Scholar 

  35. Zhang, H., Kolb, F. A., Jaskiewicz, L., Westhof, E., and Filipowicz, W. (2004). Single processing center models for human Dicer and bacterial RNase III. Cell 118, 57-68.

    Article  CAS  PubMed  Google Scholar 

  36. Zuker, M. (2003). Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31, 3406-3415.

    Article  CAS  PubMed  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 Science + Business Media B.V

About this chapter

Cite this chapter

Kozlowski, P., Starega-Roslan, J., Legacz, M., Magnus, M., Krzyzosiak, W.J. (2008). Structures of MicroRNA Precursors. In: Ying, SY. (eds) Current Perspectives in microRNAs (miRNA). Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8533-8_1

Download citation

Publish with us

Policies and ethics