TY - JOUR

T1 - Gene Expression Analysis of Yeast Strains with a Nonsense Mutation in the eRF3-Coding Gene Highlights Possible Mechanisms of Adaptation

AU - Данилов, Лаврентий Глебович

AU - Журавлева, Галина Анатольевна

AU - Максютенко, Е.М.

AU - Барбитов, Юрий Александрович

AU - Матвеенко, Андрей Георгиевич

AU - Землянко, Ольга Михайловна

AU - Ефремова, Елена Павловна

AU - Москаленко, Светлана Евгеньевна

PY - 2024/6/7

Y1 - 2024/6/7

N2 - In yeast Saccharomyces cerevisiae, there are two translation termination factors, eRF1 (Sup45) and eRF3 (Sup35), which are essential for viability. Previous studies have revealed that presence of nonsense mutations in these genes leads to amplification of mutant alleles ( sup35-n and sup45-n), which appears to be necessary for the viability of such cells. However, the mechanism of this phenomenon remained unclear. In this study, we used RNA-Seq and proteome analysis to reveal the complete set of gene expression changes that occur during cellular adaptation to the introduction of the sup35-218 nonsense allele. Our analysis demonstrated significant changes in the transcription of genes that control the cell cycle: decreases in the expression of genes of the anaphase promoting complex APC/C ( APC9, CDC23) and their activator CDC20, and increases in the expression of the transcription factor FKH1, the main cell cycle kinase CDC28, and cyclins that induce DNA biosynthesis. We propose a model according to which yeast adaptation to nonsense mutations in the translation termination factor genes occurs as a result of a delayed cell cycle progression beyond the G2-M stage, which leads to an extension of the S and G2 phases and an increase in the number of copies of the mutant sup35-n allele.

AB - In yeast Saccharomyces cerevisiae, there are two translation termination factors, eRF1 (Sup45) and eRF3 (Sup35), which are essential for viability. Previous studies have revealed that presence of nonsense mutations in these genes leads to amplification of mutant alleles ( sup35-n and sup45-n), which appears to be necessary for the viability of such cells. However, the mechanism of this phenomenon remained unclear. In this study, we used RNA-Seq and proteome analysis to reveal the complete set of gene expression changes that occur during cellular adaptation to the introduction of the sup35-218 nonsense allele. Our analysis demonstrated significant changes in the transcription of genes that control the cell cycle: decreases in the expression of genes of the anaphase promoting complex APC/C ( APC9, CDC23) and their activator CDC20, and increases in the expression of the transcription factor FKH1, the main cell cycle kinase CDC28, and cyclins that induce DNA biosynthesis. We propose a model according to which yeast adaptation to nonsense mutations in the translation termination factor genes occurs as a result of a delayed cell cycle progression beyond the G2-M stage, which leads to an extension of the S and G2 phases and an increase in the number of copies of the mutant sup35-n allele.

KW - Adaptation, Physiological/genetics

KW - Cell Cycle/genetics

KW - Codon, Nonsense/genetics

KW - Gene Expression Regulation, Fungal

KW - Peptide Termination Factors/genetics

KW - Saccharomyces cerevisiae Proteins/genetics

KW - Saccharomyces cerevisiae/genetics

UR - https://www.mendeley.com/catalogue/33dd21b9-5dba-3b07-b341-93f7015dcd07/

U2 - 10.3390/ijms25126308

DO - 10.3390/ijms25126308

M3 - Article

C2 - 38928012

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 12

M1 - 6308

ER -