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Publication Abstract from PubMed

Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding RNAs (lncRNAs) with a binding preference for G-quadruplex RNA. In this work, we present a 3.3-A-resolution cryo-electron microscopy structure of PRC2 bound to a G-quadruplex RNA. Notably, RNA mediates the dimerization of PRC2 by binding both protomers and inducing a protein interface composed of two copies of the catalytic subunit EZH2, thereby blocking nucleosome DNA interaction and histone H3 tail accessibility. Furthermore, an RNA-binding loop of EZH2 facilitates the handoff between RNA and DNA, another activity implicated in PRC2 regulation by RNA. We identified a gain-of-function mutation in this loop that activates PRC2 in zebrafish. Our results reveal mechanisms for RNA-mediated regulation of a chromatin-modifying enzyme.

Structural basis for inactivation of PRC2 by G-quadruplex RNA.,Song J, Gooding AR, Hemphill WO, Love BD, Robertson A, Yao L, Zon LI, North TE, Kasinath V, Cech TR Science. 2023 Sep 22;381(6664):1331-1337. doi: 10.1126/science.adh0059. Epub 2023 , Sep 21. PMID:37733873^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.