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

Marina Reixachs-Solé, Jorge Ruiz-Orera, M Mar Alba, Eduardo Eyras

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May 03, 2019
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Received Date: 12th April 19

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 translational level conserved between human and mouse. Furthermore, orthologous cassette exons preserving the directionality of the change were found enriched in microexons in a comparison between glia and glioma, and were conserved between human and mouse. 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 ones. ORQAS is available at https://github.com/comprna/orqas

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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