Mol. Cell https://doi.org/10.1016/j.molcel.2019.06.030 (2019)
Ribosomes interact with various factors to enable the biogenesis of newly synthesized polypeptides, including the nascent polypeptide-associated complex (NAC) and the translocon Sec61. It’s generally thought that these ribosome-associated protein biogenesis factors don’t interact with nascent polypeptides until they exit the ribosome tunnel. However, a new study by Gamerdinger et al. challenges the concept. Through structural analysis of the reconstituted Caenorhabditis elegans NAC-60S ribosomal complex and site-specific crosslinking experiments, the authors revealed that the N terminus of the β subunit of NAC (N-βNAC) inserts deeply into the ribosomal tunnel to contact nascent peptide chains upon their synthesis and are then pushed out of the ribosome tunnel together. A NAC mutant with GFP fused to the N terminus of βNAC that has lost the ability to insert into the channel fails to rescue the embryonic lethal phenotype induced by loss of NAC, suggesting that the tunnel-sensing activity of N-βNAC is essential for its biological function. This study suggests a new type of co-translational regulatory event and lays a foundation for further investigation into the ribosome-associated protein networks.