Domains of RNA-binding protein Ssd1 required for tolerating chromosome amplification in yeast

RNA-binding protein Ssd1 is crucial for yeast to maintain cellular fitness when carrying extra chromosomes, a phenomenon known as aneuploidy. This protein possesses multiple distinct domains, but the specific functions of many of these domains remain unclear. These domains encompass RNA binding folds, signals for nuclear import and export, an intrinsically disordered domain, a region that interacts with RNA polymerase II, numerous phosphorylation sites, and potential phase separation or interaction with the kinase Cbk1, which regulates Ssd1 granule formation during the cell cycle.

Researchers conducted a mutational analysis of Ssd1 to pinpoint the domains responsible for tolerating extra chromosomes. They evaluated various phenotypes, with a focus on the ability to survive with an additional copy of yeast chromosome XII, serving as a typical aneuploid. The findings revealed that mutations affecting RNA binding domains compromised cellular fitness in aneuploid cells but not in those with the correct number of chromosomes.

Conversely, alterations in phase separation or interaction with Cbk1 did not impact aneuploidy tolerance.

Analyzing correlations among the diverse growth phenotypes provided insights into the functional relationships between the different domains of Ssd1. The study's results highlight the importance of specific domains within Ssd1 for the cell's ability to tolerate aneuploidy and contribute to a better understanding of this protein's role in yeast's response to extra chromosomes.