Amino Acid Animals Computational Biology Databases de novo gene DNA Evolution Genetic Genome human Humans Mice Molecular Molecular Sequence Data Proteins Proteins: chemistry Proteins: genetics Repetitive Sequences ribosome profiling RNA-Seq Selection Sequence Analysis Sequence Homology transcriptomics yeast
2019 |
Marina Reixachs-Sole, Jorge Ruiz-Orera, M.Mar Albà, Eduardo Eyras bioRxiv, March 19, 2019. (Abstract | Links | BibTeX | Tags: human, isoform, mouse, nervous system, ribosome profiling) @article{Reixachs-Sole2019, title = {Ribosome profiling at isoform level reveals an evolutionary conserved impact of differential splicing on the proteome}, author = {Marina Reixachs-Sole, Jorge Ruiz-Orera, M.Mar Albà, Eduardo Eyras}, url = {https://doi.org/10.1101/582031 }, year = {2019}, date = {2019-03-19}, journal = {bioRxiv, March 19}, abstract = {The differential production of transcript isoforms from gene loci is a key mechanism in multiple biological processes and pathologies. Although this has been exhaustively shown at RNA level, it remains elusive at protein level. Here, we describe a new pipeline ORQAS (ORF quantification pipeline for alternative splicing) 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 50% in mouse, with 53% of the expressed genes having more than one translated isoform in human, and 33% in mouse. Differential analysis revealed that about 40% of the splicing changes measured at RNA level in human were concordant with changes in translation; and that 21.7% of changes measured at RNA level, and 17.8% at translation level, were 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 in both, and were conserved between human and mouse.. In summary, we established a moderate but widespread impact of differential splicing in the translation of isoforms and found evidence of an impact on the translation of microexons as a consequence of differential splicing. ORQAS is available at https://github.com/comprna/orqas .}, keywords = {human, isoform, mouse, nervous system, ribosome profiling} } The differential production of transcript isoforms from gene loci is a key mechanism in multiple biological processes and pathologies. Although this has been exhaustively shown at RNA level, it remains elusive at protein level. Here, we describe a new pipeline ORQAS (ORF quantification pipeline for alternative splicing) 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 50% in mouse, with 53% of the expressed genes having more than one translated isoform in human, and 33% in mouse. Differential analysis revealed that about 40% of the splicing changes measured at RNA level in human were concordant with changes in translation; and that 21.7% of changes measured at RNA level, and 17.8% at translation level, were 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 in both, and were conserved between human and mouse.. In summary, we established a moderate but widespread impact of differential splicing in the translation of isoforms and found evidence of an impact on the translation of microexons as a consequence of differential splicing. ORQAS is available at https://github.com/comprna/orqas . |
