Journal article

Regulation of constitutive and alternative mRNA splicing across the human transcriptome by PRPF8 is determined by 5 ' splice site strength

Vihandha O Wickramasinghe, Mar Gonzalez-Porta, David Perera, Arthur R Bartolozzi, Christopher R Sibley, Martina Hallegger, Jernej Ule, John C Marioni, Ashok R Venkitaraman

Genome Biology | BMC | Published : 2015

Abstract

BACKGROUND: Sequential assembly of the human spliceosome on RNA transcripts regulates splicing across the human transcriptome. The core spliceosome component PRPF8 is essential for spliceosome assembly through its participation in ribonucleoprotein (RNP) complexes for splice-site recognition, branch-point formation and catalysis. PRPF8 deficiency is linked to human diseases like retinitis pigmentosa or myeloid neoplasia, but its genome-wide effects on constitutive and alternative splicing remain unclear. RESULTS: Here, we show that alterations in RNA splicing patterns across the human transcriptome that occur in conditions of restricted cellular PRPF8 abundance are defined by the altered spl..

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Grants

Awarded by UK Medical Research Council


Awarded by Medical Research Council


Funding Acknowledgements

We thank Jon Pines (Gurdon Institute, Cambridge) and Chris Sullivan (University of Texas) for the gift of reagents, and James Hadfield and members of the sequencing facility (Cambridge Institute) for NGS. We gratefully acknowledge funding from the EMBL (MGP, JCM), and UK Medical Research Council grants 5PP00, RG60494 and RG63652 to ARV (supporting VOW, DP, ARB). Work in ARV's laboratory is funded by the UK Medical Research Council.