Prediction of Mammalian MicroRNA Targets

Benjamin Lewis, Massachusetts Institute of Technology

MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by basepairing to mRNAs to specify posttranscriptional repression of these messages [1]. However, the mRNAs regulated by vertebrate miRNAs are all unknown. We have predicted 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 [2]. 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.

References:

[1] Bartel DP. Related Articles, Links Abstract MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004 Jan 23;116(2):281-97. Review.

[2] Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Related Articles, Links Abstract Prediction of mammalian microRNA targets. Cell. 2003 Dec 26;115(7):787-98.

Abstract Author(s): Benjamin P. Lewis, I-hung Shih, Matthew W. Jones-Rhoades, David P. Bartel, and Christopher B. Burge