Cotranslational sorting and processing of newly synthesized proteins in eukaryotes.

Precise and efficient processing of nascent polypeptides by appropriate ribosome-associated factors is essential for proper protein function and localization. Recent studies demonstrate that nascent chain binding by cotranslational factors is precisely orchestrated and not only triggered by random collisions of the factors with translating ribosomes. Newly synthesized proteins are sorted at the ribosomal tunnel exit and directed into specific cotranslational protein biogenesis pathways. The nascent polypeptide-associated complex (NAC) is important for the regulation of cotranslational processing. Ribosomes interact with a variety of different protein biogenesis factors that guide newly synthesized proteins to their native 3D shapes and cellular localization. Depending on the type of translated substrate, a distinct set of cotranslational factors must interact with the ribosome in a timely and coordinated manner to ensure proper protein biogenesis. While cytonuclear proteins require cotranslational maturation and folding factors, secretory proteins must be maintained in an unfolded state and processed cotranslationally by transport and membrane translocation factors. Here we explore the specific cotranslational processing steps for cytonuclear, secretory, and membrane proteins in eukaryotes and then discuss how the nascent polypeptide-associated complex (NAC) cotranslationally sorts these proteins into the correct protein biogenesis pathway. [ABSTRACT FROM AUTHOR]