Consequences for Pancreatic β-Cell Identity and Function of Unregulated Transcript Processing
Year: 2021
Type: review
Abstract: 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.
Source: Frontiers in Endocrinology
Authors: Seyed M. Ghiasi, Guy A. Rutter
Institution: Imperial College London
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: Investigating the role of immature beta cells in insulin release from the intact islet, G1335979935, G1635243398, Genetic and nutritional control of pancreatic beta cell identity., G1937207371, Roles of GWA genes in controlling pancreatic beta cell function and mass., Control of glucagon secretion by AMPK and related kinases., G3346581055, G3555667338, G3700981753, G434337789, Assessing risk and progression of prediabetes and type 2 diabetes to enable disease modification - Sofia ref.: 115881, G4426574518, G4781795914, All-optical deconstruction of the islet wiring patterns underlying insulin secretion in health and disease, Targeting etiologic molecular mechanisms to treat human diabetes, G5673545276, The impact of long non-coding RNA at the Pax6 locus on beta cell identity and function, G6133425169, Defining the molecular and physiological mechanisms of pancreatic islet dysfunction which lead to type 2 diabetes, G6693145033, Molecular mechanisms linking Sorcin to pancreatic beta cell lipotoxicity and ER Ca2+ stores., G7328074751, G8152984508, Roles of the type 2 diabetes (T2D)-associated gene C2cd4a in regulating glucose homeostasis in the mouse
OpenAlex ID: W3135663312