Abstract 1247 Having a NAC for nascent protein biogenesis at the ribosome

The ribosome exit site is a crowded environment where numerous ribosome-associated protein biogenesis machinery (RPB) jostle for access to the nascent polypeptide. These RPBs directs the nascent polypeptide to distinct biogenesis pathways including folding, assembly, localization, maturation, and quality control. How diverse RPBs spatiotemporally coordinate with one another to triage the nascent protein is not well understood. In this talk, I will discuss recent results that suggest a key role of the nascent polypeptide associated complex (NAC), an abundant ribosome-bound chaperone conserved across eukaryotic organisms. We demonstrate a new role of NAC in enabling N-terminal acetylation, a ubiquitous protein modification that occurs on 80% of the human proteome. Together with recent reports on NAC-mediated recruitment of signal recognition particle (SRP) and potentially additional RPBs, our results suggest that NAC acts as a molecular assembly hub at the ribosome exit site that controls the access of the nascent protein to diverse protein biogenesis machinery, thus comprising an early decision point during protein biogenesis. This work was supported by National Institutes of Health grant R35 GM136321 to S.-o. Shan, the German ScienceFoundation grants SFB969/A01 and A07 to E.D. and M.G.