Role for the MOV10 RNA helicase in Polycomb-mediated repression of the INK4a tumor suppressor

Several lines of evidence point to a role for non-coding RNA in transcriptional repression by Polycomb group (PcG) proteins but the precise mechanism remains unclear. Here we show that MOV10, a putative RNA helicase previously implicated in post-transcriptional gene silencing, co-purifies and interacts with components of Polycomb-repressive complex 1 (PRC1) from human cells. Endogenous MOV10 is mostly nuclear and a proportion associates with chromatin in an RNA-dependent manner. ShRNA-mediated knockdown of MOV10 in human fibroblasts leads to up-regulation of the INK4a tumor suppressor, a known target of PcG-mediated repression, accompanied by dissociation of PRC1 proteins from the locus and a reduction in trimethylation of histone H3 on lysine 27 (H3K27me3). As well as prompting reassessment of MOV10's role in other settings, our findings suggest that it is directly involved in transcriptional silencing by PcG complexes.