Nascent Protein Selection and Triage at the Ribosome Exit Site

Abstract

Proper protein biogenesis is a pre‐requisite for the generation and maintenance of a functional proteome. Accumulating data show that this process begins early, when nascent proteins begin to emerge from the ribosome. Indeed, the ribosome exit site is a crowded environment where a variety of ribosome‐associated protein biogenesis factors (RPBs) jostle for access to the nascent polypeptide. Within seconds, the nascent polypeptide must engage the correct set of factors and commit to the proper biogenesis pathway. These early decisions profoundly influence the folding, assembly, localization, maturation, and quality control of nascent proteins. This raises the question: How do these factors, which bind the ribosome at overlapping sites and prefers similar sequence features on the nascent polypeptide, compete or collaborate with one another to enable the efficient and accurate selection of nascent proteins into the proper biogenesis pathway? In this talk, I will describe recent works that begin to illustrate how the RPBs coordinate in space and time at the ribosome exit site and highlight the importance of this molecular crowding in enhancing the fidelity of individual protein biogenesis pathways.

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