Abstract
Extreme overproduction of gratuitous proteins can overload cellular protein production resources, leading to growth defects, a phenomenon known as the protein burden/cost effect. Genetic screening in the budding yeast Saccharomyces cerevisiae has isolated several dubious ORFs whose deletions mitigated the protein burden effect, but individual characterization thereof has yet to be delineated. We found that deletion of the YJL175W ORF yielded an N-terminal deletion of Swi3, a subunit of the SWI/SNF chromatin remodeling complex, and partial loss of function of Swi3. The deletion mutant showed a reduction in transcription of genes encoding highly expressed, secreted proteins and an overall reduction in translation. Mutations in the chromatin remodeling complex could thus mitigate the protein burden effect, likely by reallocating residual cellular resources used to overproduce proteins. This cellular state might also be related to cancer cells, as they frequently harbor mutations in the SWI/SNF complex.
Highlights
Expression levels of intracellular proteins are tightly controlled to maintain organism capacity for proliferation and survival, and an excess of proteins can cause cellular dysfunction[1,2,3]
Upon isolating a series of deletion and temperature-sensitive mutants harboring genetic interactions affecting the overproduction of GFP (GFP-op) in the budding yeast Saccharomyces cerevisiae, we found that the deletion of certain uncharacterized ORFs mitigated growth defects triggered by GFP-op
If the score is negative, the growth defect triggered by GFP-op is aggravated
Summary
Expression levels of intracellular proteins are tightly controlled to maintain organism capacity for proliferation and survival, and an excess of proteins can cause cellular dysfunction[1,2,3]. Any harmless protein inhibits cell growth when it is extremely overproduced, because it depletes cellular protein production resources. This phenomenon is known as the protein burden/cost effect[3,4,5,6]. The protein burden effect is triggered by the cost of gene expression upon overexpression of gratuitous proteins; the overexpression overloads cellular transcription and translation resources[4,9]. We characterized the yeast deletion mutants in which the growth defects triggered by GFP-op are mitigated, and revealed that one of the deletion mutants unexpectedly created an N-terminal deletion of SWI3, a component of the SWI/SNF complex, and a reduction in transcription levels of certain genes. We thereby suggest that transcriptional alterations may free up ribosomes to accept ectopically expressed mRNA for translation and mitigate the protein burden effect
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
