title: Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.
abstract: MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. 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 miRNAs. 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.
authors.affiliation: Rosetta Inpharmatics, Merck and Co, 401 Terry Avenue N, Seattle, Washington 98109, USA. lee_lim@merck.com
authors.forename: Lee P
authors.initials: LP
authors.lastname: Lim
authors.forename: Nelson C
authors.initials: NC
authors.lastname: Lau
authors.forename: Philip
authors.initials: P
authors.lastname: Garrett-Engele
authors.forename: Andrew
authors.initials: A
authors.lastname: Grimson
authors.forename: Janell M
authors.initials: JM
authors.lastname: Schelter
authors.forename: John
authors.initials: J
authors.lastname: Castle
authors.forename: David P
authors.initials: DP
authors.lastname: Bartel
authors.forename: Peter S
authors.initials: PS
authors.lastname: Linsley
authors.forename: Jason M
authors.initials: JM
authors.lastname: Johnson
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D015536:Down-Regulation; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger