Poster Presentation Australasian RNA Biology and Biotechnology Association 2024 Conference

The evolution of transcriptome complexity using Oxford Nanopore long-read sequencing technology.  (#166)

Gabriela Santos-Rodriguez 1 , Akanksha Srivastava 2 , Favour Oyelami 2 , Agin Ravindran 2 , Chi Kin Ip 3 , Pallavi Gupta 4 , Jeannette Villanueva 5 , Helen Elizabeth King 3 , Abigail Grootveld 3 , Ishaan Gupta 4 , Graziele Vieira 3 , Nikolay Shirokikh 2 , Eduardo Eyras 2 , Robert James Weatheritt 3
  1. University of New South Wales, Sydney, NSW, Australia
  2. Australian National University, Canberra, NSW, Australia
  3. Garvan Institute of Medical Research, Sydney, NSW, Australia
  4. Indian Institute of Technology, Delhi, India
  5. Victor Chang Cardiac Research Institute, Sydney, NSW, Australia

The increase of biological complexity is partly due to the dynamic generation of unique cell-specific transcriptomes. Co- and post-transcriptional mechanisms including alternative splicing (AS), alternative promotor usage (APU); alternative polyadenylation (APA) have been identified as major drivers of transcriptome diversity and are known to drive lineage-specific phenotypic effects. However, this research is limited to the assessment of individual events (exons / 3’UTRs) due to the limitations of short-read sequencing  

To gain insight into the conservation of full-length transcript expression and the coordinated regulation of post-transcriptional mechanisms, we used Oxford Nanopore long-read sequencing technology to analyse isoform conservation across six tissues from five mammalian species and an outgroup. We found that multiple transcript isoforms have conserved tissue-specific expression, where >40% of the analysed genes in mammals had conserved transcripts with major isoform switching in a tissue-specific manner. Additionally, we studied the evolutionary conservation of coordinate-splicing events (the co-association of splicing events in the same transcript). We found that mammalian conserved events are depleted in mutually exclusive coordinate-splicing events and enriched in mutually associated events (present in the same transcript) and with a strong enrichment for tissue-specific expression. Together, our work uncovers extensive conservation of post-transcriptional regulation and provides a resource for understanding the transcriptome conservation across mammalian evolution.