Publication List

@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}
}

@article{Ruiz-Orera2016,
title = {Functional and non-functional classes of peptides produced by long non-coding RNAs},
author = {Jorge Ruiz-Orera, Pol Verdaguer-Grau, José Luis Villanueva-Cañas, Xavier Messeguer, M Mar Albà},
url = {http://biorxiv.org/content/early/2016/07/21/064915},
isbn = {http://dx.doi.org/10.1101/064915 },
year = {2016},
date = {2016-07-21},
journal = {bioRxiv},
abstract = {Cells express thousands of transcripts that show weak coding potential. Known as long non-coding RNAs (lncRNAs), they typically contain short open reading frames (ORFs) having no homology with known proteins. Recent studies have reported that a significant proportion of lncRNAs are translated, challenging the view that they are essentially non-coding. These results are based on the selective sequencing of ribosome-protected fragments, or ribosome profiling. The present study used ribosome profiling data from eight mouse tissues and cell types, combined with ~330,000 synonymous and non-synonymous single nucleotide variants, to dissect the biological implications of lncRNA translation. Using the three-nucleotide read periodicity that characterizes actively translated regions, we found that about 23% of the transcribed lncRNAs was translated (1,365 out of 6,390). About one fourth of the translated sequences (350 lncRNAs) showed conservation in humans; this is likely to produce functional micropeptides, including the recently discovered myoregulin. For other lncRNAs, the ORF codon usage bias distinguishes between two classes. The first has significant coding scores and contains functional proteins which are not conserved in humans. The second large class, comprising >500 lncRNAs, produces proteins that show no significant purifying selection signatures. We showed that the neutral translation of these lncRNAs depends on the transcript expression level and the chance occurrence of ORFs with a favorable codon composition. This provides the first evidence to data that many lncRNAs produce non-functional proteins.},
keywords = {long non-coding RNA, micropeptide, mouse, ribosome profiling, smORF, translation}
}