A single mutation in ACTR8 gene results in lineage-specific expression in primates

Abstract

Background: Alternative splicing (AS) generate various transcripts from a single gene and thus plays a significant role in transcriptomic diversity and proteomic complexity. Alu elements are primate-specific transposable elements (TEs) and can provide a donor or acceptor site for AS. In a study on TE-mediated AS, we recently identified a novel Alu Sz6-exonized ACTR8 transcript of a crab-eating monkey ( Macaca fascicularis ). In the present study, we sought to analyse the molecular mechanism of Alu Sz6-derived exonization in ACTR8 gene.Results: We performed RT-PCR and genomic PCR using the tissue RNA and DNA samples from the crab-eating monkey and various other primates, including humans, to study Alu Sz6-derived exonization in ACTR8 gene and transcript variants expression. Alu Sz6 integration was estimated to have occurred before the divergence of simians and prosimians. The novel transcript was expressed only in Old world monkeys and apes, and humans. Lineage-specific expression of ACTR8 gene was due to a ‘G’ duplication in the Alu Sz6 sequences of Old world monkey and ape lineages. Six alternative transcripts (TV1-TV6) generated by various AS mechanisms were newly identified. Based on in-silico analysis, the alternative transcripts were transcribed into new isoforms with C-terminus deletion.Conclusion: ‘G’ duplication together with TE exonization and AS via various mechanisms resulted in a different fate of ACTR8 gene expression during primate evolution.