Structural basis for inactivation of PRC2 by G-quadruplex RNA

• 成果类型: Article
• 署名作者: Song, Jiarui; Gooding, Anne R.; Hemphill, Wayne O.; Love, Brittney D.; Robertson, Anne; Yao, Liqi; Zon, Leonard I.; North, Trista E.; Kasinath, Vignesh; Cech, Thomas R.
• 署名单位: University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; Howard Hughes Medical Institute; Harvard University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8594
• DOI: 10.1126/science.adh0059
• 发表日期: 2023-09-22
• 页码: 1331-1337
• 关键词: complex; chromatin; RECRUITMENT; binding; ezh2; dna; methylation; refinement; jarid2; tools

摘要

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-angstrom-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.