Regulation of Alternative Splicing during Mouse Organ Development

We study the role of alternative splicing (AS) in the development of the body, as well as the search for potential AS regulators responsible for tissue-specific age-related changes in splicing. This study allowed us to conclude that in certain pairs of tissues, such as brain–cerebellum and liver–kidney, changes in splicing of the same exons occur more often than in the other pairs. There is also a higher coherence in the directions of splicing changes in those tissues. At the same time, some pairs of tissues synchronously change splicing in only one direction, for example, both tissues more often increase inclusion of exons over time in transcripts in comparison with other tissues. The liver and kidney have the most manifest tendency to simultaneously exclude cassette exon during the development of an organism. GO enrichment analysis showed that genes containing such exons, in addition to the same biological role in the development of two tissues, are responsible for the self-regulation of AS in these tissues. AS is regulated by splicing factors; therefore, the expression of genes that could potentially be them is considered in this work. Genes encoding proteins containing RNA-binding motifs change expression over time more often than other genes, which confirms their regulatory role. Exons, next to which there are motifs recognized by such proteins, are change AS much more often compared to all observed exons in general. Moreover, certain motives regulate AS in the whole set of proteins that are important for embryonic development.