Prediction of mammalian microRNA targets.
MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by basepairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5' region of the miRNA and evaluating the number and quality of these complementary sites. Rigorous tests using shuffled miRNA controls supported a majority of these predictions, with the fraction of false positives estimated at 31% for targets identified in human, mouse, and rat and 22% for targets identified in pufferfish as well as mammals. Eleven predicted targets (out of 15 tested) were supported experimentally using a HeLa cell reporter system. The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
Lewis
Benjamin P
BP
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Shih
I-hung
IH
Jones-Rhoades
Matthew W
MW
Bartel
David P
DP
Burge
Christopher B
CB
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000465:Algorithms; D000818:Animals; D016477:Artifacts; D019295:Computational Biology / Q000379:methods; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics*; D018390:Gene Targeting / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D008322:Mammals; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008967:Molecular Biology / Q000379:methods; D011237:Predictive Value of Tests; D034622:RNA Interference / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics* / Q000302:isolation & purification*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger