RNA exploits an exposed regulatory site to inhibit the enzymatic activity of PRC2.

Autor: Zhang Q; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia., McKenzie NJ; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia., Warneford-Thomson R; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Graduate Group in Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Gail EH; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia., Flanigan SF; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia., Owen BM; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia., Lauman R; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Graduate Group in Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Levina V; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia., Garcia BA; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Schittenhelm RB; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.; Monash Biomedical Proteomics Facility, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Bonasio R; Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. rbon@pennmedicine.upenn.edu.; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. rbon@pennmedicine.upenn.edu., Davidovich C; Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia. chen.davidovich@monash.edu.; EMBL-Australia and the ARC Centre of Excellence in Advanced Molecular Imaging, Clayton, Victoria, Australia. chen.davidovich@monash.edu.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2019 Mar; Vol. 26 (3), pp. 237-247. Date of Electronic Publication: 2019 Mar 04.
DOI: 10.1038/s41594-019-0197-y
Abstrakt: Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that maintains cell identity during development in multicellular organisms by marking repressed genes and chromatin domains. In addition to four core subunits, PRC2 comprises multiple accessory subunits that vary in their composition during cellular differentiation and define two major holo-PRC2 complexes: PRC2.1 and PRC2.2. PRC2 binds to RNA, which inhibits its enzymatic activity, but the mechanism of RNA-mediated inhibition of holo-PRC2 is poorly understood. Here we present in vivo and in vitro protein-RNA interaction maps and identify an RNA-binding patch within the allosteric regulatory site of human and mouse PRC2, adjacent to the methyltransferase center. RNA-mediated inhibition of holo-PRC2 is relieved by allosteric activation of PRC2 by H3K27me3 and JARID2-K116me3 peptides. Both holo-PRC2.1 and holo-PRC2.2 bind RNA, providing a unified model to explain how RNA and allosteric stimuli antagonistically regulate the enzymatic activity of PRC2.
Databáze: MEDLINE
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