The mechanisms of gene expression regulation by miRNAs have been extensively studied. However, the regulation of miRNA function and decay has long remained enigmatic. Only recently, 3′ uridylation via LIN28A-TUT4/7 has been recognized as an essential component controlling the biogenesis of let-7 miRNAs in stem cells. Although uridylation has been generally implicated in miRNA degradation, the nuclease responsible has remained unknown. Here, we identify the Perlman syndromeassociated protein DIS3L2 as an oligo(U)-binding and processing exoribonuclease that specifically targets uridylated pre-let-7 in vivo. This study establishes DIS3L2 as the missing component of the LIN28-TUT4/7-DIS3L2 pathway required for the repression of let-7 in pluripotent cells.

Graphical Abstract Highlights d First study of MICOS outside opisthokonts verifies a conserved role in shaping cristae d Trypanosome MICOS novelties include two distinct Mic10s and an atypical Mic60 d TbMICOS features a novel thioredoxin-like subunit called TbMic20 d TbMic20 appears to be a catalyst for intermembrane space protein import

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