Distinct Adaptive Mechanisms Drive Recovery from Aneuploidy Caused by Loss of the Ulp2 SUMO Protease [RNA-seq]

In response to acute loss of the Ulp2 SUMO-specific protease, yeast become disomic for chromosome I (ChrI) and ChrXII. Here we report that ChrI disomy, which creates an adaptive advantage in part by increasing the dosage of the Ccr4 deadenylase, was eliminated by extended passaging. Loss of aneuploidy is often accompanied by mutations in essential SUMO-ligating enzymes, which reduced polySUMO-conjugate accumulation. The mRNA levels for almost all ribosomal proteins increases transiently upon initial loss of Ulp2, but elevated Ccr4 levels limit excess ribosome formation. Notably, extended passaging leads to increased levels of many small nucleolar RNAs (snoRNAs) involved in ribosome biogenesis, and higher dosage of three linked ChrXII snoRNA genes suppressed ChrXII disomy in ulp2? cells. Our data reveal that aneuploidy allows rapid adaptation to Ulp2 loss, but long-term adaptation restores euploidy. Cellular evolution restores homeostasis through countervailing mutations in SUMO-modification pathways and regulatory shifts in ribosome biogenesis. Overall design: In these comparisons, the ulp2? cells either carried a WT ULP2 plasmid or empty vector and were passaged for 50 or 500 generations. mRNA profiles of them were generated by sequencing, in triplicate, using Illumina HiSeq 2500 .

49

Ryu HY, López-Giráldez F, Knight J, Hwang SS, Renner C, Kreft SG, Hochstrasser M