Analysis of synthetic genetic interactions of non-coding RNAs in Saccharomyces cerevisiae

It is now accepted that non-coding RNAs (ncRNAs) play important functional roles in the cell. Recent studies in Saccharomyces cerevisiae have identified a diverse catalogue of ncRNAs, where the majority of which a function has yet to be ascribed. Large scale phenotypic screening and transcriptional analysis using the yeast ncRNAs deletion collection have identified ncRNAs responsible for major fitness changes in rich and minimal media. Here, to understand the interplay between these non-coding RNAs, the synthetic genetic array (SGA) methodology was employed to shed light on the epistasis and plasticity of key ncRNAs in different environmental conditions. Thirty-eight ncRNA query strains were crossed with a library of 411 ncRNAs deletion mutant strains, encompassing CUTs, SUTs, snoRNAs and tRNAs. Over 1000 significant genetic interactions were observed. Unlike the protein SGA genetic interaction network, for which the majority of interactions are negative, the ncRNAs mostly displayed positive epistasis (~90.2%). Interestingly, in the presence of stressors, a significant increase in negative interactions was observed, suggesting that these ncRNAs may have environmentally dependent functions or may differentially regulate neighbouring genes in different conditions. The vast majority of ncRNA interactions (>90%) did not correlate with the epistasis of their neighbouring protein coding genes, suggesting that the ncRNA and protein interaction networks are mainly independent. The two U3 paralogues, SNR17A and SNR17B, responsible for 18S rRNA processing, share the majority of genetic interactions in rich medium as expected. However, a surprising large number of unique epistatic interactions were observed for these two snoRNAs when grown in stressful conditions, suggesting that SNR17A and SNR17B may have other roles in the cell under different environmental pressures and may have sub-functionalised after genome duplication, likely driven by environmental adaptation. Additionally, SUT480 was found to interact with SNR17A and its function was linked to the processing of 18S rRNA. ### Competing Interest Statement The authors have declared no competing interest.