Robust identification of Ptbp1-dependent splicing events by a junction-centric approach in Xenopus laevis

Abstract : Regulation of alternative splicing is an important process for cell differentiation and development. Down-regulation of Ptbp1, a regulatory RNA-binding protein, leads to developmental skin defects in Xenopus laevis. To identify Ptbp1-dependent splicing events potentially related to the phenotype, we conducted RNAseq experiments following Ptbp1 depletion. We systematically compared exon-centric and junction-centric approaches to detect differential splicing events. We showed that the junction-centric approach performs far better than the exon-centric approach in Xenopus laevis. We carried out the same comparisons using simulated data in human, which led us to propose that the better performances of the junction-centric approach in Xenopus laevis essentially relies on an incomplete exonic annotation associated with a correct transcription unit annotation. We assessed the capacity of the exon-centric and junction-centric approaches to retrieve known and to discover new Ptbp1-dependent splicing events. Notably, the junction-centric approach identified Ptbp1-controlled exons in agfg1, itga6, actn4, and tpm4 mRNAs, which were independently confirmed. We conclude that the junction-centric approach allows for a more complete and informative description of splicing events, and we propose that this finding might hold true for other species with incomplete annotations.
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Developmental Biology, Elsevier, 2017, 426 (2), pp.449-459. 〈10.1016/j.ydbio.2016.08.021〉
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Maud Noiret, Agnès Méreau, Gaelle Angrand, Marion Bervas, Carole Gautier-Courteille, et al.. Robust identification of Ptbp1-dependent splicing events by a junction-centric approach in Xenopus laevis. Developmental Biology, Elsevier, 2017, 426 (2), pp.449-459. 〈10.1016/j.ydbio.2016.08.021〉. 〈hal-01533247〉

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