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TitleStructural basis for inactivation of PRC2 by G-quadruplex RNA.
Journal, issue, pagesScience, Vol. 381, Issue 6664, Page 1331-1337, Year 2023
Publish dateSep 22, 2023
AuthorsJiarui Song / Anne R Gooding / Wayne O Hemphill / Brittney D Love / Anne Robertson / Liqi Yao / Leonard I Zon / Trista E North / Vignesh Kasinath / Thomas R Cech /
PubMed AbstractPolycomb 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 ...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.
External linksScience / PubMed:37733873 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 3.4 Å
Structure data

29578

8fyh

EMDB-29578, PDB-8fyh:
G4 RNA-mediated PRC2 dimer
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-29647: Body1 of G4 RNA-mediated PRC2 dimer from multibody refinement
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-29656: Body2 of G4 RNA-mediated PRC2 dimer from multibody refinement
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsGENE REGULATION / PRC2 / G-quadruplex RNA / RNP complex / chromatin modifier

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