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J Cell Sci. 2019 Apr 25;132(8). pii: jcs230201. doi: 10.1242/jcs.230201.

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

Author information

1
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
2
Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), 14558 Nuthetal, Germany.
3
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Laboratory of RNA Biochemistry, Takustrasse 6, 14195 Berlin, Germany florian.heyd@fu-berlin.de.

Abstract

Alternative splicing (AS) strongly increases proteome diversity and functionality in eukaryotic cells. Protein secretion is a tightly controlled process, especially when it occurs in a tissue-specific and differentiation-dependent manner. While previous work has focussed on transcriptional and post-translational regulatory mechanisms, the impact of AS on the secretory pathway remains largely unexplored. Here, we integrate results from 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 membrane trafficking using morpholino and CRISPR/Cas9 experiments. We furthermore show that these events are highly tissue-specific and mediate an adaptation of 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.

KEYWORDS:

Alternative splicing; Protein secretion; Secretory pathway; Tissue-specific adaptation

PMID:
30890649
DOI:
10.1242/jcs.230201

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