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

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 dysregulation of PAX6 α cell target genes and corresponding α cell dysfunction, including blunted glucagon secretion. These findings illustrate a distinct mechanism by which a pancreatic lncRNA can coordinate glucose homeostasis by cell-specific regulation of a broadly expressed transcription factor.
PMID: 31607563 [PubMed - as supplied by publisher]

Source: Cell Metabolism - October 8, 2019 Category: Cytology Authors: Singer RA, Arnes L, Cui Y, Wang J, Gao Y, Guney MA, Burnum-Johnson KE, Rabadan R, Ansong C, Orr G, Sussel L Tags: Cell Metab Source Type: research