| Title: |
Roles for the long non-coding RNA Pax6os1/PAX6-AS1 in pancreatic beta cell function |
| Authors: |
Lopez-Noriega L.; Callingham R.; Martinez-Sanchez A.; Nawaz S.; Pizza G.; Haberman N.; Cvetesic N.; Nguyen-Tu M. -S.; Lenhard B.; Marchetti P.; Piemonti L.; de Koning E.; Shapiro A. M. J.; Johnson P. R.; Leclerc I.; Hastoy B.; Gauthier B. R.; Pullen T. J.; Rutter G. A. |
| Contributors: |
Lopez-Noriega, L.; Callingham, R.; Martinez-Sanchez, A.; Nawaz, S.; Pizza, G.; Haberman, N.; Cvetesic, N.; Nguyen-Tu, M. -S.; Lenhard, B.; Marchetti, P.; Piemonti, L.; De Koning, E.; Shapiro, A. M. J.; Johnson, P. R.; Leclerc, I.; Hastoy, B.; Gauthier, B. R.; Pullen, T. J.; Rutter, G. A. |
| Publisher Information: |
Elsevier Inc. |
| Publication Year: |
2025 |
| Subject Terms: |
Cell biology; Cellular physiology; Molecular biology |
| 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: |
info:eu-repo/semantics/altIdentifier/wos/WOS:001397044500001; volume:28; issue:1; numberofpages:19; journal:ISCIENCE; https://hdl.handle.net/20.500.11768/177176 |
| DOI: |
10.1016/j.isci.2024.111518 |
| Availability: |
https://hdl.handle.net/20.500.11768/177176; https://doi.org/10.1016/j.isci.2024.111518; https://www.cell.com/iscience/fulltext/S2589-0042(24)02745-7?_returnURL=https://linkinghub.elsevier.com/retrieve/pii/S2589004224027457?showall=true |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.B3BDA15D |
| Database: |
BASE |