Revealing RCOR2 as a regulatory component of nuclear speckles.

CoREST CoREST2 Membrane-less organelles Nuclear speckles RCOR2 SC35 SON SRRM2 SRSF2 SRSF7

Journal

Epigenetics & chromatin
ISSN: 1756-8935
Titre abrégé: Epigenetics Chromatin
Pays: England
ID NLM: 101471619

Informations de publication

Date de publication:
24 11 2021
Historique:
received: 20 10 2021
accepted: 31 10 2021
entrez: 25 11 2021
pubmed: 26 11 2021
medline: 14 1 2022
Statut: epublish

Résumé

Nuclear processes such as transcription and RNA maturation can be impacted by subnuclear compartmentalization in condensates and nuclear bodies. Here, we characterize the nature of nuclear granules formed by REST corepressor 2 (RCOR2), a nuclear protein essential for pluripotency maintenance and central nervous system development. Using biochemical approaches and high-resolution microscopy, we reveal that RCOR2 is localized in nuclear speckles across multiple cell types, including neurons in the brain. RCOR2 forms complexes with nuclear speckle components such as SON, SRSF7, and SRRM2. When cells are exposed to chemical stress, RCOR2 behaves as a core component of the nuclear speckle and is stabilized by RNA. In turn, nuclear speckle morphology appears to depend on RCOR2. Specifically, RCOR2 knockdown results larger nuclear speckles, whereas overexpressing RCOR2 leads to smaller and rounder nuclear speckles. Our study suggests that RCOR2 is a regulatory component of the nuclear speckle bodies, setting this co-repressor protein as a factor that controls nuclear speckles behavior.

Sections du résumé

BACKGROUND
Nuclear processes such as transcription and RNA maturation can be impacted by subnuclear compartmentalization in condensates and nuclear bodies. Here, we characterize the nature of nuclear granules formed by REST corepressor 2 (RCOR2), a nuclear protein essential for pluripotency maintenance and central nervous system development.
RESULTS
Using biochemical approaches and high-resolution microscopy, we reveal that RCOR2 is localized in nuclear speckles across multiple cell types, including neurons in the brain. RCOR2 forms complexes with nuclear speckle components such as SON, SRSF7, and SRRM2. When cells are exposed to chemical stress, RCOR2 behaves as a core component of the nuclear speckle and is stabilized by RNA. In turn, nuclear speckle morphology appears to depend on RCOR2. Specifically, RCOR2 knockdown results larger nuclear speckles, whereas overexpressing RCOR2 leads to smaller and rounder nuclear speckles.
CONCLUSION
Our study suggests that RCOR2 is a regulatory component of the nuclear speckle bodies, setting this co-repressor protein as a factor that controls nuclear speckles behavior.

Identifiants

pubmed: 34819154
doi: 10.1186/s13072-021-00425-4
pii: 10.1186/s13072-021-00425-4
pmc: PMC8611983
doi:

Substances chimiques

Co-Repressor Proteins 0
Nuclear Proteins 0
Rcor2 protein, human 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

51

Subventions

Organisme : NICHD NIH HHS
ID : R01 HD097665
Pays : United States

Informations de copyright

© 2021. The Author(s).

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Auteurs

Carlos Rivera (C)

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Avenida Del Libertador Bernardo O'Higgins 340, 8320000, Santiago, Chile.
Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 6624, Boston, MA, 02114, USA.
Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, 02114, USA.

Daniel Verbel-Vergara (D)

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Avenida Del Libertador Bernardo O'Higgins 340, 8320000, Santiago, Chile.

Duxan Arancibia (D)

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Avenida Del Libertador Bernardo O'Higgins 340, 8320000, Santiago, Chile.

Anna Lappala (A)

Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 6624, Boston, MA, 02114, USA.
Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, 02114, USA.

Marcela González (M)

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Avenida Del Libertador Bernardo O'Higgins 340, 8320000, Santiago, Chile.

Fabián Guzmán (F)

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Avenida Del Libertador Bernardo O'Higgins 340, 8320000, Santiago, Chile.

Gianluca Merello (G)

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Avenida Del Libertador Bernardo O'Higgins 340, 8320000, Santiago, Chile.

Jeannie T Lee (JT)

Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 6624, Boston, MA, 02114, USA. lee@molbio.mgh.harvard.edu.
Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, 02114, USA. lee@molbio.mgh.harvard.edu.

María Estela Andrés (ME)

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Avenida Del Libertador Bernardo O'Higgins 340, 8320000, Santiago, Chile. mandres@bio.puc.cl.

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Classifications MeSH