Poster abstracts
Poster number 151 submitted by Jacob Smith
De novo analysis reveals alternative splicing induced by ATF6 and the UPR
Jacob W Smith (Chemistry and Biochemistry, The Ohio State University), Vladislav Belyy (Chemistry and Biochemistry, The Ohio State University)
Abstract:
The Unfolded Protein Response (UPR) is a eukaryotic stress response pathway that is heavily involved with nearly every aspect of development and health, and the UPR is primarily induced by three ER membrane-resident sensor proteins that detect imbalances in ER homeostasis. While the transcriptional effects of the UPR and its sensor proteins have been well-studied, alternative splicing has been underappreciated and infrequently investigated in the context of ER stress. We created a de novo method for identifying changes in splicing from long-read transcriptomics data and used it to find splicing changes induced by the UPR. This method is capable of identifying and quantifying novel splice isoforms, including those created by non-canonical splicing events. Using this method revealed that ER stress induced numerous changes in RNA splicing with a strong preference towards intron retention. We also found that one of the UPR sensors, ATF6, is necessary and sufficient to trigger alternative splicing of many of the affected genes, which span a broad range of cellular functions and protein types. Taken together, our results indicate that the UPR is altering mRNA splicing as well as transcriptional expression in response to ER stress.
Keywords: Splicing, Stress, Transcriptomics