Oral Presentation 41st Lorne Genome Conference 2020

Ribosome profiling at isoform level reveals an evolutionary conserved impact of differential splicing on the proteome (#9)

Marina Reixachs-Solé (Student Award Winner) 1 , Jorge Ruiz-Orera 2 , M Mar Albà 3 4 5 , Eduardo Eyras 1 3 4 6
  1. John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia
  2. Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
  3. IMIM - Hospital del Mar Medical Research Institute., Barcelona, Spain
  4. Catalan Institution for Research and Advanced Studies. , Barcelona, Spain
  5. Universitat Pompeu Fabra, Barcelona, Spain
  6. European Molecular Biology Laboratory (EMBL) , Canberra, ACT, Australia

The differential production of transcript isoforms from gene loci is a key cellular mechanism. Yet, its impact in protein production remains an open question. Here, we describe ORQAS (ORF quantification pipeline for alternative splicing), a new pipeline for the translation quantification of individual transcript isoforms using ribosome-protected mRNA fragments (Ribosome profiling). We found evidence of translation for 40-50% of the expressed transcript isoforms in human and mouse, with 53% of the expressed genes having more than one translated isoform in human, 33% in mouse. Differential analysis revealed that about 40% of the splicing changes at RNA level were concordant with changes in translation, with 21.7% of changes at RNA level and 17.8% at translation level conserved between human and mouse. Furthermore, orthologous cassette exons preserving the directionality of the change were conserved between human and mouse and enriched in microexons in a comparison between glia and glioma. ORQAS leverages ribosome profiling to uncover a widespread and evolutionary conserved impact of differential splicing on the translation of isoforms and, in particular, of microexon-containing isoforms. ORQAS is available at https://github.com/comprna/orqas

 

 Student Award sponsored by

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