MicroRNAs 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.
Wu
Ligang
L
Skirball Institute of Biomolecular Medicine and Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Fan
Jihua
J
Belasco
Joel G
JG
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D012315:RNA Caps / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; D012315:RNA Caps; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human