Vladimir Babenko
Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia
bob [at] bionet.nsc.ru
Abstract
Based on publicly available RNA-seq data of human hippocampus samples, we identified alternatively spliced (AS) exons genome wide along with assessing the genes percentage spliced in (psi) values. The data has been compiled on more than 30 samples for each gene. Along with psi values we compiled pairwise covariation matrix across all AS (exon skipping) exons based on Pearson r2. Further Agglomerative Hierarchical Clustering (AHC) procedure on matrix revealed dense AS exons clusters with linked exons, with clusters size in the iterval of [2..19] (pairwise correlation pvalue<1E-6). There were around 2200 genes with clusters of coordinated AS exons.
Further analysis revealed AS clusters maintain antagonistic or independent relations within a gene. We explored the traits of genes abundant with AS clusters: the majority proved to be neurospecific genes, including synapse, and cytoskeletal (axonal) genes. Notably, Neurospecific splice factors (SFs) also maintain expanded coordinated AS regulation.
While the previous study observed coordinated splicing before [1], the scale of the phenomenon has not been explicitly highlighted. From the evolutionary point of view, and, given the information complexity of splicing decreases upon exon co-varitaion, we may speculate that the rapid response to the homeostatic environment favors quick coordinated splicing mediated tune-up of the gene’s isoform. Still, the mechanistic background of phenonenon is not elucidated. One of the viable hypothesis is the specific secondary structure of mRNA favoring the quick coordinated SFs binding.
In our report we address the phenomenon and consider several examples of coordinated AS.
Keywords: AS exons co-variation, coordinated alternative splicing within a gene, AS exons cluster, AS mediated information complexity
Acknowledgement: This work has been supported by ICG SB RAS state program.