Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs (original) (raw)

Nature volume 433, pages 769–773 (2005)Cite this article

Abstract

MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals1,2. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3′ untranslated regions of these messages had a significant propensity to pair to the 5′ region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs3. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.

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Figure 1: Tissue-specific gene expression rankings for downregulated genes.

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Figure 2: Over-represented motifs in the 3′ UTRs of downregulated genes.

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Figure 3: Microarray analysis of the effects of miRNA mutations.

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Figure 4: MicroRNA-directed repression of renilla luciferase reporter genes bearing 3′ UTR segments from predicted target genes.

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Acknowledgements

Thanks to S. Baskerville, M. Cleary and P. Sharp for comments on the manuscript, C. Armour, S. Bartz, J. Burchard, G. Cavet, D. Haynor, A. Jackson, M. Pellegrini, E. Schadt and Y. Wang for their assistance, the Rosetta Gene Expression Laboratory for microarray work, M. Jones-Rhoades for primer design, and W. Johnston for plasmid construction.

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Authors and Affiliations

  1. Rosetta Inpharmatics (wholly owned subsidiary of Merck and Co.), 401 Terry Avenue N, Seattle, Washington, 98109, USA
    Lee P. Lim, Philip Garrett-Engele, Janell M. Schelter, John Castle, Peter S. Linsley & Jason M. Johnson
  2. Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts, 02142, USA
    Nelson C. Lau, Andrew Grimson & David P. Bartel

Authors

  1. Lee P. Lim
  2. Nelson C. Lau
  3. Philip Garrett-Engele
  4. Andrew Grimson
  5. Janell M. Schelter
  6. John Castle
  7. David P. Bartel
  8. Peter S. Linsley
  9. Jason M. Johnson

Corresponding author

Correspondence toLee P. Lim.

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The authors declare that they have no competing financial interests.

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Lim, L., Lau, N., Garrett-Engele, P. et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.Nature 433, 769–773 (2005). https://doi.org/10.1038/nature03315

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Editorial Summary

microRNAs edit the message

New work on microRNAs (miRNAs) sheds light on the nature of tissue-specific gene expression in humans. miRNAs act in plants and animals to regulate gene expression. Microarray analysis of messenger RNAs expressed in human cells containing miR-124, an miRNA expressed in the brain, or miR-1, found in muscle, shows that the miRNAs skew a cell's expression profile to resemble that of the miRNA's ‘home’ cells, regardless of source. This involves the downregulation of many target mRNA transcripts, as well as reduction of the amount of protein produced.