Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Cell Rep. 2012 Dec 27;2(6):1537-45. doi: 10.1016/j.celrep.2012.10.023. Epub 2012 Nov 29.
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.
微小 RNA(miRNA)是一种小的非编码 RNA,可以抑制翻译并促进 mRNA 降解。成熟 miRNA 的水平是转录、加工和周转速率不同的结果。非典型聚合酶 Gld2 被认为参与了 miR-122 的稳定,可能是通过催化 3'单腺苷酸化;然而,几乎没有证据表明这种关系是因果关系。在这里,我们从生化角度描述了 Gld2 参与 miRNA 单腺苷酸化及其对 miRNA 稳定性的影响。我们发现 Gld2 直接单腺苷酸化并稳定人成纤维细胞中的特定 miRNA 群体,并且对单腺苷酸化诱导的稳定性的敏感性取决于 miRNA 3'末端的核苷酸。这些结果建立了 miRNA 稳定性和随后的转录后基因调控的机制。