Abstract
Since messenger RNAs without a stop codon (nonstop mRNAs) for organelle-targeted proteins and their translation products (nonstop proteins) generate clogged translocon channels as well as stalled ribosomes, cells have mechanisms to degrade nonstop mRNAs and nonstop proteins and to clear the translocons (e.g. the Sec61 complex) by release of nonstop proteins into the organellar lumen. Here we followed the fate of nonstop endoplasmic reticulum (ER) membrane proteins with different membrane topologies in yeast to evaluate the importance of the Ltn1-dependent cytosolic degradation and the Dom34-dependent release of the nonstop membrane proteins. Ltn1-dependent degradation differed for membrane proteins with different topologies and its failure did not affect ER protein import or cell growth. On the other hand, failure in the Dom34-dependent release of the nascent polypeptide from the ribosome led to the block of the Sec61 channel and resultant inhibition of other protein import into the ER caused cell growth defects. Therefore, the nascent chain release from the translation apparatus is more instrumental in clearance of the clogged ER translocon channel and thus maintenance of normal cellular functions.
Highlights
Proteins are under the elaborate surveillance to maintain cellular protein homeostasis
We first asked if nonstop endoplasmic reticulum (ER) membrane proteins are under the surveillance for cytosolic ubiquitination followed by proteasomal degradation
We addressed the questions of how ER-targeted membrane proteins are handled by the ribosome-based cellular protein quality control mechanisms when their translation encounters aberrant situations such as a lack of a stop codon
Summary
Proteins are under the elaborate surveillance to maintain cellular protein homeostasis. Generation of stalled RNC complexes calls for the nonstop-decay (NSD) pathway to degrade nonstop mRNAs and ribosomal quality control (RQC) factors to deal with nonstop proteins and recycle the stalled ribosomes[1,2,3]. We found that, when degradation of nonstop mRNAs does not work efficiently, nonstop proteins targeted to the ER or mitochondria occupy translating ribosomes and translocons (translocators) in the organellar membranes[13]. The cytosolic RQC pathway, which is important for the clearance of nonstop proteins in the cytosol, may not operate sufficiently for those nonstop proteins targeted to the ER and mitochondria. We asked which of the pathways, the cytosolic Ltn1-dependent degradation and the Dom34-Hbs[1] dependent release into the ER lumen, nonstop ER membrane proteins can be targeted to. We followed the fate of nonstop membrane proteins at the ER membrane with different membrane topologies, and found that the latter pathway is more important for the quality control of nonstop membrane proteins at the ER membrane
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
