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The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA
Inserm UMRS 1131, Institut de Génétique Moléculaire, Université de Paris, Hôpital St. Louis, Paris, France.
Inserm UMRS 1131, Institut de Génétique Moléculaire, Université de Paris, Hôpital St. Louis, Paris, France; University of Gdańsk, Science, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland.
Inserm UMRS 1131, Institut de Génétique Moléculaire, Université de Paris, Hôpital St. Louis, Paris, France; University of Gdańsk, Science, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland.
Inserm UMRS 1131, Institut de Génétique Moléculaire, Université de Paris, Hôpital St. Louis, Paris, France.
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2022 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 50, no 17, p. 10110-10122Article in journal (Refereed) Published
Abstract [en]

Protein aggregates and abnormal proteins are toxic and associated with neurodegenerative diseases. There are several mechanisms to help cells get rid of aggregates but little is known on how cells prevent aggregate-prone proteins from being synthesised. The EBNA1 of the Epstein-Barr virus (EBV) evades the immune system by suppressing its own mRNA translation initiation in order to minimize the production of antigenic peptides for the major histocompatibility (MHC) class I pathway. Here we show that the emerging peptide of the disordered glycine-alanine repeat (GAr) within EBNA1 dislodges the nascent polypeptide-associated complex (NAC) from the ribosome. This results in the recruitment of nucleolin to the GAr-encoding mRNA and suppression of mRNA translation initiation in cis. Suppressing NAC alpha (NACA) expression prevents nucleolin from binding to the GAr mRNA and overcomes GAr-mediated translation inhibition. Taken together, these observations suggest that EBNA1 exploits a nascent protein quality control pathway to regulate its own rate of synthesis that is based on sensing the nascent GAr peptide by NAC followed by the recruitment of nucleolin to the GAr-encoding RNA sequence.

Place, publisher, year, edition, pages
Oxford University Press, 2022. Vol. 50, no 17, p. 10110-10122
National Category
Biochemistry and Molecular Biology
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URN: urn:nbn:se:umu:diva-200116DOI: 10.1093/nar/gkac751ISI: 000853923900001PubMedID: 36107769Scopus ID: 2-s2.0-85138487767OAI: oai:DiVA.org:umu-200116DiVA, id: diva2:1702578
Funder
Cancerforskningsfonden i NorrlandSwedish Cancer Society, 160598Swedish Research CouncilAvailable from: 2022-10-11 Created: 2022-10-11 Last updated: 2023-05-23Bibliographically approved

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Chen, SaFåhraeus, Robin

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