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G-tract RNA removes Polycomb repressive complex 2 from genes

Beltran, M; Tavares, M; Justin, N; Khandelwal, G; Ambrose, J; Foster, BM; Worlock, KB; ... Jenner, RG; + view all (2019) G-tract RNA removes Polycomb repressive complex 2 from genes. Nature Structural & Molecular Biology 10.1038/s41594-019-0293-z. (In press).

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Abstract

Polycomb repressive complex 2 (PRC2) maintains repression of cell-type-specific genes but also associates with genes ectopically in cancer. While it is currently unknown how PRC2 is removed from genes, such knowledge would be useful for the targeted reversal of deleterious PRC2 recruitment events. Here, we show that G-tract RNA specifically removes PRC2 from genes in human and mouse cells. PRC2 preferentially binds G tracts within nascent precursor mRNA (pre-mRNA), especially within predicted G-quadruplex structures. G-quadruplex RNA evicts the PRC2 catalytic core from the substrate nucleosome. In cells, PRC2 transfers from chromatin to pre-mRNA upon gene activation, and chromatin-associated G-tract RNA removes PRC2, leading to H3K27me3 depletion from genes. Targeting G-tract RNA to the tumor suppressor gene CDKN2A in malignant rhabdoid tumor cells reactivates the gene and induces senescence. These data support a model in which pre-mRNA evicts PRC2 during gene activation and provides the means to selectively remove PRC2 from specific genes.

Type: Article
Title: G-tract RNA removes Polycomb repressive complex 2 from genes
Location: United States
DOI: 10.1038/s41594-019-0293-z
Publisher version: https://doi.org/10.1038/s41594-019-0293-z
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. - Correction issued dated 6 November 2019 (https://doi.org/10.1038/s41594-019-0341-8).
Keywords: Cancer, Epigenetics, RNA
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10082438
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