title: Cotranslational microRNA mediated messenger RNA destabilization.
abstract: MicroRNAs are small (22 nucleotide) regulatory molecules that play important roles in a wide variety of biological processes. These RNAs, which bind to targeted mRNAs via limited base pairing interactions, act to reduce protein production from those mRNAs. Considerable evidence indicates that miRNAs destabilize targeted mRNAs by recruiting enzymes that function in normal mRNA decay and mRNA degradation is widely thought to occur when mRNAs are in a ribosome free state. Nevertheless, when examined, miRNA targeted mRNAs are invariably found to be polysome associated; observations that appear to be at face value incompatible with a simple decay model. Here, we provide evidence that turnover of miRNA-targeted mRNAs occurs while they are being translated. Cotranslational mRNA degradation is initiated by decapping and proceeds 5' to 3' behind the last translating ribosome. These results provide an explanation for a long standing mystery in the miRNA field.
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, United States.
authors.forename: Trinh To
authors.initials: TT
authors.lastname: Tat
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, United States.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Maroney
authors.affiliation: Affymetrix, Inc., Cleveland, United States.
authors.forename: Sangpen
authors.initials: S
authors.lastname: Chamnongpol
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, United States.
authors.forename: Jeff
authors.initials: J
authors.lastname: Coller
authors.affiliation: Center for RNA Molecular Biology, Case Western Reserve University, Cleveland, United States.
authors.forename: Timothy W
authors.identifier: 0000-0002-7276-3571
authors.initials: TW
authors.lastname: Nilsen
mesh_terms: D000818:Animals; D002460:Cell Line; D004330:Drosophila; D035683:MicroRNAs / Q000378:metabolism*; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: D. melanogaster; chromosomes; cotranslation; genes; mRNA decay; microRNAs