Specific miRNA Stabilization by Gld2-Catalyzed Monoadenylation

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. [Display omitted] ► Gld2 monoadenylates specific microRNAs (miRNAs) ► Monoadenylation stabilizes miRNA subpopulations and prolongs their activity ► Sensitivity to monoadenylation and stability depends on nucleotides in the miRNA 3′ end MicroRNA (miRNA) levels are the result of regulated transcription, processing, and turnover. Recent deep-sequencing studies found that miRNAs appended with additional nucleotides that are not derived from their genomic sequences. Here, Richter and colleagues characterize the noncanonical polymerase Gld2’s involvement in miRNA monoadenylation and its effect on miRNA stability. They find that Gld2 directly monoadenylates and stabilizes specific miRNAs, and that sensitivity to monoadenylation-induced stability depends on nucleotides in the miRNA 3′ ends. These results establish a mechanism of miRNA stability and resulting posttranscriptional gene regulation.