| Title: |
Consequences for pancreatic beta-cell identity and function of unregulated transcript processing |
| Authors: |
Ghiasi, SM; Rutter, GA |
| Contributors: |
MRC Programme Grant |
| Source: |
12 ; 1 |
| Publisher Information: |
Frontiers Media |
| Publication Year: |
2021 |
| Collection: |
Imperial College London: Spiral |
| Subject Terms: |
Science & Technology; Life Sciences & Biomedicine; Endocrinology & Metabolism; β; cell; insulin secretion; transcript; nonsense-mediated decay; RNA decay; RNA processing; β-cell; 1103 Clinical Sciences; 1111 Nutrition and Dietetics |
| Description: |
Mounting evidence suggests a role for alternative splicing (AS) of transcripts in the normal physiology and pathophysiology of the pancreatic β-cell. In the apparent absence of RNA repair systems, RNA decay pathways are likely to play an important role in controlling the stability, distribution and diversity of transcript isoforms in these cells. Around 35% of alternatively spliced transcripts in human cells contain premature termination codons (PTCs) and are targeted for degradation via nonsense-mediated decay (NMD), a vital quality control process. Inflammatory cytokines, whose levels are increased in both type 1 (T1D) and type 2 (T2D) diabetes, stimulate alternative splicing events and the expression of NMD components, and may or may not be associated with the activation of the NMD pathway. It is, however, now possible to infer that NMD plays a crucial role in regulating transcript processing in normal and stress conditions in pancreatic β-cells. In this review, we describe the possible role of Regulated Unproductive Splicing and Translation (RUST), a molecular mechanism embracing NMD activity in relationship to AS and translation of damaged transcript isoforms in these cells. This process substantially reduces the abundance of non-functional transcript isoforms, and its dysregulation may be involved in pancreatic β-cell failure in diabetes. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Frontiers in Endocrinology; http://hdl.handle.net/10044/1/87783; MR/R022259/1 |
| DOI: |
10.3389/fendo.2021.625235 |
| Availability: |
http://hdl.handle.net/10044/1/87783; https://doi.org/10.3389/fendo.2021.625235 |
| Rights: |
© 2021 Ghiasi and Rutter. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.E0A8F839 |
| Database: |
BASE |