Letters to Nature

Nature 433, 769-773 (17 February 2005) | doi:10.1038/nature03315; Received 22 July 2004; Accepted 22 December 2004; Published online 30 January 2005

Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs

Lee P. Lim1, Nelson C. Lau2, Philip Garrett-Engele1, Andrew Grimson2, Janell M. Schelter1, John Castle1, David P. Bartel2, Peter S. Linsley1 & Jason M. Johnson1

  1. Rosetta Inpharmatics (wholly owned subsidiary of Merck and Co.), 401 Terry Avenue N, Seattle, Washington 98109, USA
  2. Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA

Correspondence to: Lee P. Lim1 Correspondence and requests for materials should be addressed to L.P.L. (Email: lee_lim@merck.com).
The GEO accession number for the microarray data is GSE2075.

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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