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.

• MeSH
• alanin MeSH
• fosfoproteiny MeSH
• glycin MeSH
• infekce virem Epsteina-Barrové * MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• peptidy genetika   MeSH
• proteinové agregáty MeSH
• proteiny vázající RNA metabolismus   MeSH
• virus Epsteinův-Barrové - jaderné antigeny metabolismus   MeSH
• virus Epsteinův-Barrové * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dítě MeSH
• kojenecká mortalita MeSH
• lidé MeSH
• příčina smrti MeSH
• Check Tag
• dítě MeSH
• lidé MeSH