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

Nature Structural & Molecular Biology volume 17, pages 862–868 (2010)Cite this article

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Abstract

Several lines of evidence point to a role for noncoding RNA in transcriptional repression by Polycomb group (PcG) proteins, but the precise mechanism remains unclear. Here we show that human 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 human MOV10 is mostly nuclear, and a proportion associates with chromatin in an RNA-dependent manner. Small hairpin RNA (shRNA)-mediated knockdown of MOV10 in human fibroblasts leads to the upregulation of the INK4a tumor suppressor, a known target of PcG-mediated repression, accompanied by the dissociation of PRC1 proteins from the locus and a reduction in trimethylation of histone H3 on Lys27 (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.

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Figure 1: Interaction of MOV10 with CBX7.
Figure 2: MOV10 is predominantly nuclear and associated with chromatin.
Figure 3: MOV10 co-precipitates with multiple PRC1 components.
Figure 4: MOV10 contributes to the regulation of INK4a in primary fibroblasts.
Figure 5: MOV10 contributes to the transcriptional repression of INK4a by the Pc proteins.
Figure 6: Lack of interaction between MOV10 and PRC2 components.

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Acknowledgements

We are indebted to M. Rodriguez-Niedenführ and J. Rowe for substantial contributions to the project and to other members of the Molecular Oncology laboratory for helpful discussions, H. Koseki (RIKEN Research Center for Allergy and Immunology) and J. Gil (Medical Research Council Clinical Sciences Centre) for the generous gift of reagents, N. O'Reilly for help with peptide synthesis and antibody production, N. Totty for MS, C. Esnault for advice on ChIP and D. Ish-Horowicz for insightful comments on the manuscript.

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Authors and Affiliations

  1. Cancer Research UK, London Research Institute, London, UK

    Selma El Messaoudi-Aubert, James Nicholls, Goedele N Maertens, Sharon Brookes & Gordon Peters

  2. Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York, USA

    Emily Bernstein

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  1. Selma El Messaoudi-Aubert
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Contributions

S.E.M.-A. performed most of the experiments described in the manuscript and drafted the figures and text; J.N. characterized the mCbx7 complex and, together with E.B., provided the initial evidence for the interaction with MOV10; G.N.M. assisted with the gel-filtration analyses; S.B. performed the immunofluorescence; G.P. directed the project and prepared the manuscript.

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Correspondence to Gordon Peters.

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Messaoudi-Aubert, S., Nicholls, J., Maertens, G. et al. Role for the MOV10 RNA helicase in Polycomb-mediated repression of the INK4a tumor suppressor. Nat Struct Mol Biol 17, 862–868 (2010). https://doi.org/10.1038/nsmb.1824

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