[
International Worm Meeting,
2021]
Alternative splicing plays a major role in establishing tissue-specific transcriptomes and contributing to tissue identity and function. Our lab has previously identified hundreds of isoforms that exhibit distinct splicing patterns across broad tissue types in the C. elegans L4 stage. Echoing observations from comparative analyses of splicing regulation in vertebrates, our data also demonstrates that tissue-regulated alternative exons are more likely to be frame-preserving and are enriched in specific cis-regulatory motifs when compared with constitutively spliced exons. Second, regulated exons are more often shorter than constitutive exons, but are flanked by longer intron sequences. Intriguingly, our analysis has also identified examples of highly conserved alternatively spliced microexons less than 27 nucleotides in length. Finally, alternatively spliced exons also overlap less frequently with conserved protein domains than constitutively spliced exons but overlap more frequently with intrinsically disordered regions, which are emerging as important peptide sequences controlling the localization, In this study, we have expanded our analysis of tissue-regulated splicing across developmental stages, augmenting our L4 data with embryonic and adult transcriptomes from various tissues. Our results have identified several hundred splice variants regulated in a temporal manner in specific tissues. Interestingly, a significant number of temporally-regulated splicing events have already adopted their adult-stage splicing pattern by late embryogenesis, suggesting early developmental patterning of splicing during cell differentiation to terminal states. Using this data, we are isolating putative RNA binding proteins that direct the splicing of co-regulated genes and examining the functional differences that arise in these protein isoforms to contribute to tissue development. Collectively, our results indicate an important and rich layer of spatio-temporal gene regulation at the level of alternative splicing in C. elegans.