Pre-emptive Quality Control of a Misfolded Membrane Protein by Ribosome-Driven Effects.

ABSTRACT: Cells possess multiple mechanisms that protect against the accumulation of toxic aggregation-prone proteins. Here, we identify a pre-emptive pathway that reduces synthesis of membrane proteins that have failed to properly assemble in the endoplasmic reticulum (ER). We show that loss of the ER membrane complex (EMC) or mutation of the Sec61 translocon causes reduced synthesis of misfolded forms of the yeast ABC transporter Yor1. Synthesis defects are rescued by various ribosomal mutations, as well as by reducing cellular ribosome abundance. Genetic and biochemical evidence point to a ribosome-associated quality-control pathway triggered by ribosome collisions when membrane domain insertion and/or folding fails. In support of this model, translation initiation also contributes to synthesis d

SUBMITTER: Lakshminarayan R 

PROVIDER: S-EPMC7063571 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature