Seminars

“Chaperone-mediated regulation of translation in the mammalian stress response”
Abstract:
Protein homeostasis is one of the core principles that living organisms strive to maintain. When protein homeostasis is perturbed, cells across all kingdoms unanimously respond by shutting down protein synthesis and upregulating molecular chaperones in an effort to cope with misfolding and aggregation. Investigating translation regulation genome-wide during the heat shock response, I discovered a novel mode of translational control: translation elongation pausing. Elongation pausing appears to be a major part of the translational response to proteotoxic stress in mammalian cells, affecting nearly all mRNAs, shortly after the encoded nascent peptide emerges from the ribosome exit tunnel. Elongation pausing is mediated by Hsp70 chaperones, and their dynamic association with the ribosome, which is downregulated in heat shock. It is therefore emerging that chaperone association with the ribosome serves to regulate translation, highlighting the importance of chaperone-ribosome cross-talk in protecting cells from proteotoxic stress.