Volume 20, Issue S2 p. 77-87
REVIEW ARTICLE

When one becomes many—Alternative splicing in β-cell function and failure

Maria Inês Alvelos

Maria Inês Alvelos

ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium

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Jonàs Juan-Mateu PhD

Jonàs Juan-Mateu PhD

ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium

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Maikel Luis Colli MD, PhD

Maikel Luis Colli MD, PhD

ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium

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Jean-Valéry Turatsinze PhD

Jean-Valéry Turatsinze PhD

ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium

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Décio L. Eizirik MD, PhD

Corresponding Author

Décio L. Eizirik MD, PhD

ULB Center for Diabetes Research and Welbio, Medical Faculty, Université Libre de Bruxelles (ULB), Brussels, Belgium

Correspondence

Décio L. Eizirik, Medical Faculty, ULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), Route de Lennik, 808—CP618, B-1070 Brussels, Belgium.

Email: deizirik@ulb.ac.be

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First published: 19 September 2018
Citations: 30
Funding information E.F.P.I.A. European Federation of Pharmaceutical Industries; Fonds National de la Recherche Scientifique (FNRS), Grant/Award Number: 26410496; Innovative Medicines Initiative , Grant/Award Number: 115797 (INNODIA); Juvenile Diabetes Research Foundation International; NIDDK-supported Human Islet Research Network, Grant/Award Numbers: SCR_014393, UC4 DK104166, RRID:SCR_014393; The Leona M. and Harry B. Helmsley Charitable Trust; Fonds National de la Recherche Scientifique, Grant/Award Number: 26410496; Innovative Medicines Initiative 2 Joint Undertaking, Grant/Award Number: 115797; Horizon 2020 Program T2Dsystems, Grant/Award Number: GA667191; Belgian FRFS-Welbio, Grant/Award Number: CR-2015A-06

Abstract

Pancreatic β-cell dysfunction and death are determinant events in type 1 diabetes (T1D), but the molecular mechanisms behind β-cell fate remain poorly understood. Alternative splicing is a post-translational mechanism by which a single gene generates different mRNA and protein isoforms, expanding the transcriptome complexity and enhancing protein diversity. Neuron-specific and certain serine/arginine-rich RNA binding proteins (RBP) are enriched in β-cells, playing crucial roles in the regulation of insulin secretion and β-cell survival. Moreover, alternative exon networks, regulated by inflammation or diabetes susceptibility genes, control key pathways and processes for the correct function and survival of β-cells. The challenge ahead of us is to understand the precise role of alternative splicing regulators and splice variants on β-cell function, dysfunction and death and develop tools to modulate it.