[PDF][PDF] Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes

I Morán, I Akerman, M Van De Bunt, R Xie, M Benazra… - Cell metabolism, 2012 - cell.com
Cell metabolism, 2012cell.com
A significant portion of the genome is transcribed as long noncoding RNAs (lncRNAs),
several of which are known to control gene expression. The repertoire and regulation of
lncRNAs in disease-relevant tissues, however, has not been systematically explored. We
report a comprehensive strand-specific transcriptome map of human pancreatic islets and β
cells, and uncover> 1100 intergenic and antisense islet-cell lncRNA genes. We find islet
lncRNAs that are dynamically regulated and show that they are an integral component of the …
Summary
A significant portion of the genome is transcribed as long noncoding RNAs (lncRNAs), several of which are known to control gene expression. The repertoire and regulation of lncRNAs in disease-relevant tissues, however, has not been systematically explored. We report a comprehensive strand-specific transcriptome map of human pancreatic islets and β cells, and uncover >1100 intergenic and antisense islet-cell lncRNA genes. We find islet lncRNAs that are dynamically regulated and show that they are an integral component of the β cell differentiation and maturation program. We sequenced the mouse islet transcriptome and identify lncRNA orthologs that are regulated like their human counterparts. Depletion of HI-LNC25, a β cell-specific lncRNA, downregulated GLIS3 mRNA, thus exemplifying a gene regulatory function of islet lncRNAs. Finally, selected islet lncRNAs were dysregulated in type 2 diabetes or mapped to genetic loci underlying diabetes susceptibility. These findings reveal a new class of islet-cell genes relevant to β cell programming and diabetes pathophysiology.
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