The TGFB2-AS1 lncRNA Regulates TGF-β Signaling by Modulating Corepressor Activity.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
17 Sep 2019
Historique:
received: 11 10 2018
revised: 08 05 2019
accepted: 05 08 2019
entrez: 19 9 2019
pubmed: 19 9 2019
medline: 12 9 2020
Statut: ppublish

Résumé

Molecular processes involving lncRNAs regulate cell function. By applying transcriptomics, we identify lncRNAs whose expression is regulated by transforming growth factor β (TGF-β). Upon silencing individual lncRNAs, we identify several that regulate TGF-β signaling. Among these lncRNAs, TGFB2-antisense RNA1 (TGFB2-AS1) is induced by TGF-β through Smad and protein kinase pathways and resides in the nucleus. Depleting TGFB2-AS1 enhances TGF-β/Smad-mediated transcription and expression of hallmark TGF-β-target genes. Increased dose of TGFB2-AS1 reduces expression of these genes, attenuates TGF-β-induced cell growth arrest, and alters BMP and Wnt pathway gene profiles. Mechanistically, TGFB2-AS1, mainly via its 3' terminal region, binds to the EED adaptor of the Polycomb repressor complex 2 (PRC2), promoting repressive histone H3K27me

Identifiants

pubmed: 31533040
pii: S2211-1247(19)31062-9
doi: 10.1016/j.celrep.2019.08.028
pmc: PMC6859500
pii:
doi:

Substances chimiques

RNA, Antisense 0
RNA, Long Noncoding 0
Transforming Growth Factor beta 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3182-3198.e11

Subventions

Organisme : European Research Council
ID : 787472
Pays : International

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Panagiotis Papoutsoglou (P)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, and Ludwig Cancer Research Box 582, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.

Yutaro Tsubakihara (Y)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, and Ludwig Cancer Research Box 582, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.

Laia Caja (L)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, and Ludwig Cancer Research Box 582, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.

Anita Morén (A)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, and Ludwig Cancer Research Box 582, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.

Paris Pallis (P)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, and Ludwig Cancer Research Box 582, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.

Adam Ameur (A)

Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Box 256, Uppsala University, 751 05 Uppsala, Sweden.

Carl-Henrik Heldin (CH)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, and Ludwig Cancer Research Box 582, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden.

Aristidis Moustakas (A)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, and Ludwig Cancer Research Box 582, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden. Electronic address: aris.moustakas@imbim.uu.se.

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Classifications MeSH