| Title: |
Roles for the long non-coding RNA Pax6os1 / PAX6-AS1 in pancreatic beta cell function |
| Authors: |
Lopez-Noriega, L; Callingham, R; Martinez-Sánchez, A; Nawaz, S; Pizza, G; Haberman, N; Cvetesic, N; Nguyen-Tu, M; Lenhard, B; Marchetti, P; Piemonti, L; de Koning, E; Shapiro, AMJ; Johnson, PR; Leclerc, I; Hastoy, B; Gauthier, BR; Pullen, TJ; Rutter, GA |
| Publisher Information: |
Cell Press |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of beta cell function. Here, we show that an lncRNA-transcribed antisense to Pax6, annotated as Pax6os1/PAX6-AS1, was upregulated by high glucose concentrations in human as well as murine beta cell lines and islets. Elevated expression was also observed in islets from mice on a high-fat diet and patients with type 2 diabetes. Silencing Pax6os1/PAX6-AS1 in MIN6 or EndoC-βH1 cells increased several beta cell signature genes' expression. Pax6os1/PAX6-AS1 was shown to bind to EIF3D, indicating a role in translation of specific mRNAs, as well as histones H3 and H4, suggesting a role in histone modifications. Important interspecies differences were found, with a stronger phenotype in humans. Only female Pax6os1 null mice fed a high-fat diet showed slightly enhanced glucose clearance. In contrast, silencing PAX6-AS1 in human islets enhanced glucose-stimulated insulin secretion and increased calcium dynamics, whereas overexpression of the lncRNA resulted in the opposite phenotype. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1016/j.isci.2024.111518 |
| DOI: |
10.1016/j.isci.2024.111518 |
| Availability: |
https://doi.org/10.1016/j.isci.2024.111518; https://ora.ox.ac.uk/objects/uuid:f1ed4423-cb69-4dc9-856f-dd9ce4a7fe01 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.823ABCD1 |
| Database: |
BASE |