AUF1 ligand circPCNX reduces cell proliferation by competing with p21 mRNA to increase p21 production.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
22 02 2021
22 02 2021
Historique:
accepted:
11
12
2020
revised:
28
11
2020
received:
27
08
2020
pubmed:
15
1
2021
medline:
4
3
2021
entrez:
14
1
2021
Statut:
ppublish
Résumé
Mammalian circRNAs can influence different cellular processes by interacting with proteins and other nucleic acids. Here, we used ribonucleoprotein immunoprecipitation (RIP) analysis to identify systematically the circRNAs associated with the cancer-related protein AUF1. Among the circRNAs interacting with AUF1 in HeLa (human cervical carcinoma) cells, we focused on hsa_circ_0032434 (circPCNX), an abundant target of AUF1. Overexpression of circPCNX specifically interfered with the binding of AUF1 to p21 (CDKN1A) mRNA, thereby promoting p21 mRNA stability and elevating the production of p21, a major inhibitor of cell proliferation. Conversely, silencing circPCNX increased AUF1 binding to p21 mRNA, reducing p21 production and promoting cell division. Importantly, eliminating the AUF1-binding region of circPCNX abrogated the rise in p21 levels and rescued proliferation. Therefore, we propose that the interaction of circPCNX with AUF1 selectively prevents AUF1 binding to p21 mRNA, leading to enhanced p21 mRNA stability and p21 protein production, thereby suppressing cell growth.
Identifiants
pubmed: 33444453
pii: 6097529
doi: 10.1093/nar/gkaa1246
pmc: PMC7897478
doi:
Substances chimiques
3' Untranslated Regions
0
CDKN1A protein, human
0
Cyclin-Dependent Kinase Inhibitor p21
0
HNRNPD protein, human
0
Heterogeneous Nuclear Ribonucleoprotein D0
0
RNA, Circular
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1631-1646Subventions
Organisme : Intramural NIH HHS
ID : Z01 AG000511
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC011646
Pays : United States
Informations de copyright
Published by Oxford University Press on behalf of Nucleic Acids Research 2021.
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