Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Identification of hundreds of conserved and nonconserved human microRNAs

Abstract

MicroRNAs are noncoding RNAs of 22 nucleotides that suppress translation of target genes by binding to their mRNA and thus have a central role in gene regulation in health and disease1,2,3,4,5. To date, 222 human microRNAs have been identified6, 86 by random cloning and sequencing, 43 by computational approaches and the rest as putative microRNAs homologous to microRNAs in other species. To prove our hypothesis that the total number of microRNAs may be much larger and that several have emerged only in primates, we developed an integrative approach combining bioinformatic predictions with microarray analysis and sequence-directed cloning. Here we report the use of this approach to clone and sequence 89 new human microRNAs (nearly doubling the current number of sequenced human microRNAs), 53 of which are not conserved beyond primates. These findings suggest that the total number of human microRNAs is at least 800.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: MicroRNA detection and validation.
Figure 2: The number of conserved microRNAs in the human genome.
Figure 3: Two new nonconserved microRNA clusters.
Figure 4: Multiple sequence alignments of cloned mature microRNAs from the two new nonconserved clusters.

Accession codes

Accessions

Gene Expression Omnibus

References

  1. Ambros, V., Lee, R.C., Lavanway, A., Williams, P.T. & Jewell, D. MicroRNAs and other tiny endogenous RNAs in C. elegans . Curr. Biol. 13, 807–818 (2003).

    Article  CAS  Google Scholar 

  2. Bartel, D.P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004).

    Article  CAS  Google Scholar 

  3. Johnston, R.J. & Hobert, O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans . Nature 426, 845–849 (2003).

    Article  CAS  Google Scholar 

  4. Lim, L.P., Glasner, M.E., Yekta, S., Burge, C.B. & Bartel, D.P. Vertebrate microRNA genes. Science 299, 1540 (2003).

    Article  CAS  Google Scholar 

  5. Poy, M.N. et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432, 226–230 (2004).

    Article  CAS  Google Scholar 

  6. Griffiths-Jones, S. The microRNA registry. Nucleic Acids Res. 32, D109–D111 (2004).

    Article  CAS  Google Scholar 

  7. Barad, O. et al. MicroRNA expression detected by oligonucleotide microarrays: System establishment and expression profiling in human tissues. Genome Res. 14, 2486–2494 (2004).

    Article  CAS  Google Scholar 

  8. Lim, L.P. et al. The microRNAs of Caenorhabditis elegans . Genes Dev. 17, 991–1008 (2003).

    Article  CAS  Google Scholar 

  9. Berezikov, E. et al. Phylogenetic shadowing and computational identification of human microRNA genes. Cell 120, 21–24 (2005).

    Article  CAS  Google Scholar 

  10. Xie, X. et al. Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature 434, 338–345 (2005).

    Article  CAS  Google Scholar 

  11. Suh, M. et al. Human embryonic stem cells express a unique set of microRNAs. Dev. Biol. 270, 488–498 (2004).

    Article  CAS  Google Scholar 

  12. Houbaviy, H.B., Murray, M.F. & Sharp, P.A. Embryonic stem cell-specific microRNAs. Dev. Cell 5, 351–358 (2003).

    Article  CAS  Google Scholar 

  13. Bentwich, I. A postulated role for microRNA in cellular differentiation. FASEB J. 19, 875–879 (2005).

    Article  CAS  Google Scholar 

  14. Hofacker, I.L. Vienna RNA secondary structure server. Nucleic Acids Res. 31, 3429–3431 (2003).

    Article  CAS  Google Scholar 

  15. Siepel, A. & Haussler, D. Combining phylogenetic and hidden Markov models in biosequence analysis. J. Comput. Biol. 11, 413–428 (2004).

    Article  CAS  Google Scholar 

  16. Schwartz, S. et al. Human-mouse alignments with BLASTZ. Genome Res. 13, 103–107 (2003).

    Article  CAS  Google Scholar 

  17. Elbashir, S.M., Lendeckel, W. & Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15, 188–200 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the members of the Rosetta Genomics team for their dedication and contribution.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Isaac Bentwich.

Ethics declarations

Competing interests

The authors are employed by and own shares or options in Rosetta Genomics Ltd., a company that is involved in discovery and commercialization of microRNA.

Supplementary information

Supplementary Fig. 1

Expression profiles of novel validated microRNAs (I). (PDF 99 kb)

Supplementary Fig. 2

Expression profiles of novel validated microRNAs (II). (PDF 441 kb)

Supplementary Table 1

Novel validated microRNAs. (PDF 88 kb)

Supplementary Table 2

Microarray results for novel validated and known microRNAs. (PDF 59 kb)

Supplementary Methods (PDF 107 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bentwich, I., Avniel, A., Karov, Y. et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37, 766–770 (2005). https://doi.org/10.1038/ng1590

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1590

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing