engleski

Control of Rrp6 stability in yeast sporulation

The conserved 3'-5' exoribonuclease Rrp6 (EXOSC10 in mammals) is a catalytic subunit of the nuclear RNA exosome, which degrades and processes RNAs in eukaryotic cells. Rrp6 and EXOSC10 are important for efficient meiotic development in yeast and male and female gametogenesis in mammals, respectively. We have shown earlier that yeast Rrp6 protein levels decrease during meiotic M-phase and yeast spore formation although the mRNA continues to be expressed. Given that Rrp6/EXOSC10 undergoes a variety of post-translational modifications, including ubiquitination, we hypothesized that Rrp6 is degraded by targeted proteolysis in differentiating cells. We first confirm that Rrp6 becomes unstable when cells progress from fermentation to respiration and sporulation and then show that the protein rapidly accumulates during initial rounds of cell division after spore germination. Furthermore, we show that Rrp6 degradation requires an active Anaphase Promoting Complex/Cyclosome (APC/C). Finally, we demonstrate that an Rrp6 allele lacking the sole APC/C target motif (destruction box) conserved from yeast to humans remains detectable during sporulation. We conclude that Rrp6 protein stability is under nutritional control via targeted proteolysis by the APC/C-proteasome pathway. These results are relevant for mammals because EXOSC10 is also ubiquitinated, diminishes during spermatogenesis and becomes unstable after cold-shock via SUMOylation.

RNA exosome, Rrp6, meiosis, proteolysis, APC

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