Cells maintain proteostasis by selectively recognizing and targeting misfolded proteins for degradation. InSaccharomyces cerevisiae, the Hsp70 nucleotide exchange factor Fes1 is essential for the degradation of chaperone-associated misfolded proteins by the ubiquitin-proteasome system. Here we show that theFES1transcript undergoes unique 3' alternative splicing that results in two equally active isoforms with alternative C-termini, Fes1L and Fes1S. Fes1L is actively targeted to the nucleus and represents the first identified nuclear Hsp70 nucleotide exchange factor. In contrast, Fes1S localizes to the cytosol and is essential to maintain proteostasis. In the absence of Fes1S, the heat-shock response is constitutively induced at normally nonstressful conditions. Moreover, cells display severe growth defects when elevated temperatures, amino acid analogues, or the ectopic expression of misfolded proteins, induce protein misfolding. Importantly, misfolded proteins are not targeted for degradation by the ubiquitin-proteasome system. These observations support the notion that cytosolic Fes1S maintains proteostasis by supporting the removal of toxic misfolded proteins by proteasomal degradation. This study provides key findings for the understanding of the organization of protein quality control mechanisms in the cytosol and nucleus.
Sample name | Organism | Experiment title | Sample type | Library instrument | Attributes | |||||||||||||||||||||||||||||||||||||||||||||||||
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source name | strain | |||||||||||||||||||||||||||||||||||||||||||||||||||||
fes1DS rep 3 | Saccharomyces cerevisiae | GSM2067903: fes1DS rep 3; Saccharomyces cerevisiae; RNA-Seq | RNA-Seq | Illumina HiSeq 2500 | Yeast log phase cells | CAY1290 | ||||||||||||||||||||||||||||||||||||||||||||||||
fes1DS rep 2 | Saccharomyces cerevisiae | GSM2067902: fes1DS rep 2; Saccharomyces cerevisiae; RNA-Seq | RNA-Seq | Illumina HiSeq 2500 | Yeast log phase cells | CAY1290 | ||||||||||||||||||||||||||||||||||||||||||||||||
fes1DS rep 1 | Saccharomyces cerevisiae | GSM2067901: fes1DS rep 1; Saccharomyces cerevisiae; RNA-Seq | RNA-Seq | Illumina HiSeq 2500 | Yeast log phase cells | CAY1290 | ||||||||||||||||||||||||||||||||||||||||||||||||
fes1DL rep 3 | Saccharomyces cerevisiae | GSM2067900: fes1DL rep 3; Saccharomyces cerevisiae; RNA-Seq | RNA-Seq | Illumina HiSeq 2500 | Yeast log phase cells | CAY1256 | ||||||||||||||||||||||||||||||||||||||||||||||||
fes1DL rep 2 | Saccharomyces cerevisiae | GSM2067899: fes1DL rep 2; Saccharomyces cerevisiae; RNA-Seq | RNA-Seq | Illumina HiSeq 2500 | Yeast log phase cells | CAY1256 |