The Long Noncoding RNA Paupar Modulates PAX6 Regulatory Activities to Promote Alpha Cell Development and Function.

ABSTRACT: Many studies have highlighted the role of dysregulated glucagon secretion in the etiology of hyperglycemia and diabetes. Accordingly, understanding the mechanisms underlying pancreatic islet α cell development and function has important implications for the discovery of new therapies for diabetes. In this study, comparative transcriptome analyses between embryonic mouse pancreas and adult mouse islets identified several pancreatic lncRNAs that lie in close proximity to essential pancreatic transcription factors, including the Pax6-associated lncRNA Paupar. We demonstrate that Paupar is enriched in glucagon-producing α cells where it promotes the alternative splicing of Pax6 to an isoform required for activation of essential α cell genes. Consistently, deletion of Paupar in mice resulted in

SUBMITTER: Singer RA 

PROVIDER: S-EPMC7205457 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature