A ROLE FOR THE PERLMAN SYNDROME EXONUCLEASE DIS3L2 IN THE LIN28-LET-7 PATHWAY

摘要

The 3 '-5' exonuclease, Dis312, is responsible for the decay of uridylated pre-let-7 miRNA. Biochemical reconstitution assays revealed that 3' oligouridylation stimulates Dis312 activity in vitro, and knockdown of Dis312 in mouse embryonic stem cells leads to the stabilization of pre-let-7 miRNA. These Dis312-depleted stem cells displayed elevated expression of pluripotency genes and delayed differentiation. The present disclosure establishes 3' oligouridylation as an RNA decay signal for Dis312 and identifies the first physiological RNA substrate of this exonuclease.