Co-translational mechanisms of quality control of newly synthesized polypeptides

During protein synthesis, nascent polypeptides emerge from ribosomes to fold into functional proteins. Misfolding of newly synthesized polypeptides (NSPs) at this stage leads to their aggregation. These misfolded NSPs must be expediently cleared to circumvent the deleterious effects of protein aggregation on cell physiology. To this end, a sizable portion of NSPs are ubiquitinated and rapidly degraded by the proteasome. This suggests the existence of co-translational mechanisms that play a pivotal role in the quality control of NSPs. It is generally thought that ribosomes play a central role in this process. During mRNA translation, ribosomes sense errors that lead to the accumulation of aberrant polypeptides, and serve as a hub for protein complexes that are required for optimal folding and/or proteasome-dependent degradation of misfolded polypeptides. In this review, we discuss recent findings that shed light on the molecular underpinnings of the co-translational quality control of NSPs.