@article{ghiasi_consequences_2021, title = {Consequences for Pancreatic β-Cell Identity and Function of Unregulated Transcript Processing}, volume = {12}, issn = {1664-2392}, url = {https://www.frontiersin.org/articles/10.3389/fendo.2021.625235/full}, doi = {10.3389/fendo.2021.625235}, 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.}, pages = {625235}, journaltitle = {Frontiers in Endocrinology}, shortjournal = {Front. Endocrinol.}, author = {Ghiasi, Seyed M. and Rutter, Guy A.}, urldate = {2021-09-07}, date = {2021-03-08}, keywords = {{WP}4}, }