BioProject

Alternative splicing (AS) influences the expression of human genes in diverse ways. More...

Alternative splicing (AS) influences the expression of human genes in diverse ways. We previously used subcellular fraction-sequencing (Frac-Seq) to reveal an unexpected connection between alternative splicing and isoform-specific mRNA translation. Here we apply comparative transcriptomics to explore alternative splicing coupled translational control (AS-TC) across 13 million years of primate evolution. We used Frac-seq to identify polyribosome associated mRNA isoforms from human, chimpanzee and orangutan induced pluripotent stem cell lines. We discovered or­thologous AS-TC events with either conserved or species-specific translation patterns. Exons sequences associated with similar sedimentation profiles between species show strong sequence con­servation compared to orthologous exons with divergent sedimentation profiles, suggesting exonic cis-regulatory elements influence to translational control. To test this hypothesis we created luciferase reporters from orthologous exons with divergent sedimentation profiles differing by a single nucleotide. Remarkably, single nucleotide substitutions were sufficient to drive species-specific expression of luciferase reporters. Together these data establish that cis-acting elements regulate AS-TC across primate species. Overall design: Subcellular Fractionation and RNA sequencing Less...