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Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs.

ABSTRACT: 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 syndrome-associated 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.

SUBMITTER: Ustianenko D

PROVIDER: S-EPMC3884668 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs.

Ustianenko Dmytro D Hrossova Dominika D Potesil David D Chalupnikova Katerina K Hrazdilova Kristyna K Pachernik Jiri J Cetkovska Katerina K Uldrijan Stjepan S Zdrahal Zbynek Z Vanacova Stepanka S

RNA (New York, N.Y.) 20131018 12

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 syndrome-associated protein DIS ...[more]

PMID: 24141620

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