Ribosome profiling at isoform level reveals evolutionary conserved impacts of differential splicing on the proteome

Marina Reixachs-Solé, Jorge Ruiz-Orera, M. Mar Albà and Eduardo Eyras ()
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Marina Reixachs-Solé: Australian National University
Jorge Ruiz-Orera: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
M. Mar Albà: IMIM - Hospital del Mar Medical Research Institute
Eduardo Eyras: Australian National University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract 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 pipeline for the translation quantification of individual transcript isoforms using ribosome-protected mRNA fragments (ribosome profiling). We find evidence of translation for 40–50% of the expressed isoforms in human and mouse, with 53% of the expressed genes having more than one translated isoform in human, and 33% in mouse. Differential splicing analysis revealed that about 40% of the splicing changes at RNA level are concordant with changes in translation. Furthermore, orthologous cassette exons between human and mouse preserve the directionality of the change, and are enriched in microexons in a comparison between glia and glioma. ORQAS leverages ribosome profiling to uncover a widespread and evolutionarily conserved impact of differential splicing on translation, particularly of microexon-containing isoforms.

Date: 2020
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DOI: 10.1038/s41467-020-15634-w

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