8FYH

G4 RNA-mediated PRC2 dimer

Summary for 8FYH

• Entry DOI: 10.2210/pdb8fyh/pdb
• EMDB information: 29578 29647 29656
• Descriptor: Polycomb protein SUZ12, Polycomb protein EED, Histone-binding protein RBBP4, ... (8 entities in total)
• Functional Keywords: prc2, g-quadruplex rna, rnp complex, chromatin modifier, gene regulation
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 13
• Total formula weight: 929371.37

Authors

Song, J.,Kasinath, V. (deposition date: 2023-01-26, release date: 2023-10-04, Last modification date: 2024-10-30)

Primary citation

Song, J.,Gooding, A.R.,Hemphill, W.O.,Love, B.D.,Robertson, A.,Yao, L.,Zon, L.I.,North, T.E.,Kasinath, V.,Cech, T.R.
Structural basis for inactivation of PRC2 by G-quadruplex RNA.
Science, 381:1331-1337, 2023

PubMed Abstract: 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-Å-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.

PubMed: 37733873
DOI: 10.1126/science.adh0059

Experimental method

ELECTRON MICROSCOPY (3.4 Å)