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Dev Biol June 15, 2017; 426 (2): 449-459.
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Robust identification of Ptbp1-dependent splicing events by a junction-centric approach in Xenopus laevis.

Noiret M , Méreau A , Angrand G , Bervas M , Gautier-Courteille C , Legagneux V , Deschamps S , Lerivray H , Viet J , Hardy S , Paillard L , Audic Y .

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.

PubMed ID: 27546377
Article link: Dev Biol

Species referenced: Xenopus laevis
Genes referenced: actn1 actn4 agfg1 eef1a1 esrp1 hspg2 itga6 itgb4 ptbp1 ptbp2 sacm1l tnfaip3 tpm1 tpm4
Morpholinos: ptbp1 MO1

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