title: Specific miRNA stabilization by Gld2-catalyzed monoadenylation.
abstract: MicroRNAs (miRNAs) are small, noncoding RNAs that inhibit translation and promote mRNA decay. The levels of mature miRNAs are the result of different rates of transcription, processing, and turnover. The noncanonical polymerase Gld2 has been implicated in the stabilization of miR-122, possibly through catalyzing 3' monoadenylation; however, there is little evidence that this relationship is one of cause and effect. Here, we biochemically characterize Gld2's involvement in miRNA monoadenylation and its effect on miRNA stability. We find that Gld2 directly monoadenylates and stabilizes specific miRNA populations in human fibroblasts and that sensitivity to monoadenylation-induced stability depends on nucleotides in the miRNA 3' end. These results establish a mechanism of miRNA stability and resulting posttranscriptional gene regulation.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: D'Ambrogio
authors.forename: Weifeng
authors.initials: W
authors.lastname: Gu
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Udagawa
authors.forename: Craig C
authors.initials: CC
authors.lastname: Mello
authors.forename: Joel D
authors.initials: JD
authors.lastname: Richter
mesh_terms: D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011062:Polynucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability / Q000502:physiology*; D039221:mRNA Cleavage and Polyadenylation Factors
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse; D039221:mRNA Cleavage and Polyadenylation Factors; C575491:Gld2 protein, mouse; D011062:Polynucleotide Adenylyltransferase; C550174:TENT2 protein, human