CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation.

3' Untranslated Regions / genetics Cell Proliferation Gene Expression Regulation mRNA Cleavage and Polyadenylation Factors / genetics Neoplasms / genetics Polyadenylation Humans Cell Line, Tumor
CP: Molecular biology CP:Cancer CPSF6 alternative polyadenylation cancer cell proliferation phase separation phosphorylation

Journal

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

Informations de publication

Date de publication:
31 10 2023
Historique:
received: 15 09 2022
revised: 20 06 2023
accepted: 18 09 2023
medline: 6 11 2023
pubmed: 1 10 2023
entrez: 1 10 2023
Statut: ppublish

Résumé

Cancer cells usually exhibit shortened 3' untranslated regions (UTRs) due to alternative polyadenylation (APA) to promote cell proliferation and migration. Upregulated CPSF6 leads to a systematic prolongation of 3' UTRs, but CPSF6 expression in tumors is typically higher than that in healthy tissues. This contradictory observation suggests that it is necessary to investigate the underlying mechanism by which CPSF6 regulates APA switching in cancer. Here, we find that CPSF6 can undergo liquid-liquid phase separation (LLPS), and elevated LLPS is associated with the preferential usage of the distal poly(A) sites. CLK2, a kinase upregulated in cancer cells, destructs CPSF6 LLPS by phosphorylating its arginine/serine-like domain. The reduction of CPSF6 LLPS can lead to a shortened 3' UTR of cell-cycle-related genes and accelerate cell proliferation. These results suggest that CPSF6 LLPS, rather than its expression level, may be responsible for APA regulation in cancer cells.

Identifiants

DOI: 10.1016/j.celrep.2023.113197 PMID: 37777964
pubmed: 37777964
pii: S2211-1247(23)01209-3
doi: 10.1016/j.celrep.2023.113197
pii:
doi:

Substances chimiques

3' Untranslated Regions 0
mRNA Cleavage and Polyadenylation Factors 0
cleavage factor Im, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

113197

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Susu Liu (S)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Runze Wu (R)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Liutao Chen (L)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Ke Deng (K)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Xin Ou (X)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Xin Lu (X)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Mengxia Li (M)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Chao Liu (C)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Shangwu Chen (S)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.

Yonggui Fu (Y)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China. Electronic address: fuyg@mail.sysu.edu.cn.

Anlong Xu (A)

State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China; School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, P.R. China. Electronic address: lssxal@mail.sysu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Régions non traduites › Régions 3' non traduites › CPSF6 regulates alternative polyadenylation...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › CPSF6 regulates alternative polyadenylation...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › CPSF6 regulates alternative polyadenylation...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Facteurs de clivage et de polyadénylation de l'ARN messager › CPSF6 regulates alternative polyadenylation...
questionsmedicales.fr › Tumeurs › CPSF6 regulates alternative polyadenylation...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Maturation de l'extrémité 3' des ARN › Polyadénylation › CPSF6 regulates alternative polyadenylation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › CPSF6 regulates alternative polyadenylation...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › CPSF6 regulates alternative polyadenylation...