biostudies-literature00470Wu LNIGMS NIH HHS4034-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC1449641biostudies-literatureUnknown103(11)MicroRNAs (miRNAs) are ubiquitous regulators of eukaryotic gene expression. In addition to repressing translation, miRNAs can down-regulate the concentration of mRNAs that contain elements to which they are imperfectly complementary. Using miR-125b and let-7 as representative miRNAs, we show that in mammalian cells this reduction in message abundance is a consequence of accelerated deadenylation, which leads to rapid mRNA decay. The ability of miRNAs to expedite poly(A) removal does not result from decreased translation; nor does translational repression by miRNAs require a poly(A) tail, a 3' histone stem-loop being an effective substitute. These findings suggest that miRNAs use two distinct posttranscriptional mechanisms to down-regulate gene expression.Proceedings of the National Academy of Sciences of the United States of AmericaMicroRNAs direct rapid deadenylation of mRNA.PMC1449641GM55624R01 GM055624Wu LFan JBelasco JG47falseMicroRNAs direct rapid deadenylation of mRNA.MicroRNAs (miRNAs) are ubiquitous regulators of eukaryotic gene expression. In addition to repressing translation, miRNAs can down-regulate the concentration of mRNAs that contain elements to which they are imperfectly complementary. Using miR-125b and let-7 as representative miRNAs, we show that in mammalian cells this reduction in message abundance is a consequence of accelerated deadenylation, which leads to rapid mRNA decay. The ability of miRNAs to expedite poly(A) removal does not result from decreased translation; nor does translational repression by miRNAs require a poly(A) tail, a 3' histone stem-loop being an effective substitute. These findings suggest that miRNAs use two distinct posttranscriptional mechanisms to down-regulate gene expression.2006-01-01T00:00:00Z2006 Mar2021-03-03T08:27:18Z2019-03-27T01:26:19ZS-EPMC14496411649541210.1073/pnas.0510928103