PUBLICATION
Structural basis for inactivation of PRC2 by G-quadruplex RNA
- Authors
- 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.
- ID
- ZDB-PUB-231002-74
- Date
- 2023
- Source
- Science (New York, N.Y.) 381: 133113371331-1337 (Journal)
- Registered Authors
- North, Trista, Zon, Leonard I.
- Keywords
- none
- MeSH Terms
-
- Animals
- Cryoelectron Microscopy
- Crystallography, X-Ray
- Enhancer of Zeste Homolog 2 Protein/chemistry
- Enhancer of Zeste Homolog 2 Protein/genetics
- G-Quadruplexes*
- Gain of Function Mutation
- Histones/genetics
- Polycomb Repressive Complex 2*/chemistry
- Polycomb Repressive Complex 2*/genetics
- Promoter Regions, Genetic
- Protein Binding
- Protein Conformation
- Protein Multimerization
- RNA Precursors*
- RNA, Long Noncoding*/chemistry
- RNA, Long Noncoding*/genetics
- Zebrafish/genetics
- Zebrafish/growth & development
- PubMed
- 37733873 Full text @ Science
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. (2023) Structural basis for inactivation of PRC2 by G-quadruplex RNA. Science (New York, N.Y.). 381:133113371331-1337.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping