Abstract
Ubiquitin conjugation signals for selective protein degradation by the proteasome. In eukaryotes, ubiquitin is encoded both as a monomeric ubiquitin unit fused to a ribosomal gene and as multiple ubiquitin units in tandem. The polyubiquitin gene is a unique, highly conserved open reading frame composed solely of tandem repeats, yet it is still unclear why cells utilize this unusual gene structure. Using the Saccharomyces cerevisiae UBI4 gene, we show that this multi-unit structure allows cells to rapidly produce large amounts of ubiquitin needed to respond to sudden stress. The number of ubiquitin units encoded by UBI4 influences cellular survival and the rate of ubiquitin-proteasome system (UPS)-mediated proteolysis following heat stress. Interestingly, the optimal number of repeats varies under different types of stress indicating that natural variation in repeat numbers may optimize the chance for survival. Our results demonstrate how a variable polycistronic transcript provides an evolutionary alternative for gene copy number variation.
Highlights
Ubiquitin conjugation signals for selective protein degradation by the proteasome
Three genes encode ubiquitin as a monomeric ubiquitin unit fused to ribosomal proteins: RPL40A (UBI1); RPL40B (UBI2); and RPS31 (UBI3)[8, 10]
UBI4, encodes multiple ubiquitin units in tandem[11, 12]. Each of these fusion genes is transcribed as a single transcript and translated into ubiquitin precursors that are subsequently cleaved by specialized proteases called deubiquitinating enzymes (DUBs) to release mature ubiquitin monomers[13]
Summary
Ubiquitin conjugation signals for selective protein degradation by the proteasome. In eukaryotes, ubiquitin is encoded both as a monomeric ubiquitin unit fused to a ribosomal gene and as multiple ubiquitin units in tandem. UBI4, encodes multiple ubiquitin units in tandem[11, 12] Each of these fusion genes is transcribed as a single transcript and translated into ubiquitin precursors (i.e., a ubiquitin moiety fused to a ribosomal protein or to another ubiquitin) that are subsequently cleaved by specialized proteases called deubiquitinating enzymes (DUBs) to release mature ubiquitin monomers[13]. Expression of the polyubiquitin UBI4 gene is stress-inducible and increases after heat stress, upon exposure to DNA-damaging agents, under oxidative stress, in stationary phase and in conditions of zinc deficiency[11, 15,16,17] This regulation makes UBI4, a gene composed solely of tandem repeats, the main source of de novo ubiquitin synthesis under stress conditions. Despite extensive research on the UPS and its multiple components, the advantages of such a multi-unit gene structure, and whether the (natural) variation in the number of ubiquitin-coding units affects cell physiology have not been previously investigated
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