The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA

التفاصيل البيبلوغرافية
العنوان: The nascent polypeptide-associated complex (NAC) controls translation initiation in cis by recruiting nucleolin to the encoding mRNA
المؤلفون: Zheng, Alice J L, Thermou, Aikaterini, Daskalogianni, Chrysoula, Malbert-Colas, Laurence, Karakostis, Konstantinos, Le Sénéchal, Ronan, Trang Dinh, Van, Tovar Fernandez, Maria C., Apcher, Sébastien, Chen, Sa, 1967, Blondel, Marc, Fåhraeus, Robin
المصدر: Nucleic Acids Research. 50(17):10110-10122
الوصف: 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.
وصف الملف: electronic
URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-200116
https://doi.org/10.1093/nar/gkac751
https://umu.diva-portal.org/smash/get/diva2:1702578/FULLTEXT01.pdf
قاعدة البيانات: SwePub
الوصف
تدمد:03051048
DOI:10.1093/nar/gkac751