Nov 1, 2018

Genome-wide identification of alternative splicing events that regulate protein transport across the secretory pathway

BioRxiv : the Preprint Server for Biology
Alexander NeumannFlorian Heyd

Abstract

Alternative splicing (AS) strongly increases proteome diversity and functionality in eukaryotic cells. Protein secretion is a tightly-controlled process, especially in a tissue-specific and differentiation-dependent manner. While previous work has focussed on transcriptional and posttranslational regulatory mechanisms, the impact of AS on the secretory pathway remains largely unexplored. Here we integrate a published screen for modulators of protein transport and RNA-Seq analyses to identify over 200 AS events as secretion regulators. We confirm that splicing events along all stages of the secretory pathway regulate the efficiency of protein transport using Morpholinos and CRISPR/Cas9. We furthermore show that these events are highly tissue-specific and adapt the secretory pathway during T-cell activation and adipocyte differentiation. Our data substantially advance the understanding of AS functionality, add a new regulatory layer to a fundamental cell biological process and provide a resource of alternative isoforms that control the secretory pathway.

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Mentioned in this Paper

Genome-Wide Association Study
CRISPR-Cas Systems
Secretory Pathway
Transcription, Genetic
Regulation of Protein Transport
Protein Secretion
Protein kinase modulator
Process of Secretion
Cell Differentiation Process
T-Cell Activation

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