Department of Genetics and Development, Columbia University, New York, New York 10032, USA;
Genomic Programming of Β-Cells Laboratory, Institut d'Investigacions August Pi I Sunyer (IDIBAPS), Barcelona 08036, Spain; Department of Medicine, Imperial College London, London W12 0NN, United Kingdom.
Genes Dev. 2016 Mar 1;30(5):502-7. doi: 10.1101/gad.273821.115.
Pancreatic β cells are responsible for maintaining glucose homeostasis; their absence or malfunction results in diabetes mellitus. Although there is evidence that long noncoding RNAs (lncRNAs) play important roles in development and disease, none have been investigated in vivo in the context of pancreas development. In this study, we demonstrate that βlinc1 (β-cell long intergenic noncoding RNA 1), a conserved lncRNA, is necessary for the specification and function of insulin-producing β cells through the coordinated regulation of a number of islet-specific transcription factors located in the genomic vicinity of βlinc1. Furthermore, deletion of βlinc1 results in defective islet development and disruption of glucose homeostasis in adult mice.
胰岛β细胞负责维持葡萄糖稳态;其缺失或功能障碍会导致糖尿病。尽管有证据表明长非编码 RNA(lncRNA)在发育和疾病中发挥重要作用,但在胰腺发育的背景下,尚未有研究对其进行调查。在这项研究中,我们证明了βlinc1(β细胞长基因间非编码 RNA 1)是一种保守的 lncRNA,通过协调调节位于βlinc1基因组附近的一些胰岛特异性转录因子,对于胰岛素产生β细胞的特化和功能是必需的。此外,βlinc1 的缺失会导致成年小鼠胰岛发育缺陷和葡萄糖稳态紊乱。