IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
Human Beta-Cell Transcriptome Analysis Uncovers lncRNAs That Are Tissue-Specific, Dynamically Regulated, and Abnormally Expressed in Type 2 Diabetes
Autor/es:
MORAN, I.; AKERMAN, I.; VAN DE BUNT, M.; XIE, R.; BENAZRA, M.; NAMMO, T.; ARNES, L.; NAKIC, N.; GARCIA-HURTADO, J.; RODRIGUEZ SEGUI, S.; PASQUALI, L.; SAUTY-COLACE, C.; BEUCHER, A.; SCHARFMANN, R.; VAN ARENSBERGEN, J.; JOHNSON, P.J.; BERRY, A.; LEE, C.; HARKINS, T.; GMYR, V.; PATTOU, F.; KERR-CONTE, J.; PIEMONTI, L.; BERNEY, T.; HANLEY, N.; GLOYN, A.N.; SUSSEL, L.; LANGMAN, L.; BRAYMAN, K. L.; SANDER, M.; MCCARTHY, M.I.; RAVASSARD, P.; FERRER, J.
Revista:
CELL METABOLISM
Editorial:
CELL PRESS
Referencias:
Lugar: United States; Año: 2012 vol. 16 p. 435 - 448
ISSN:
1550-4131
Resumen:
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 transcriptomemapofhumanpancreaticislets and bcells, and uncover >1100 intergenic and antisense islet-celllncRNA genes. We find islet lncRNAs that are dynamically regulated and show that they are an integral component of the b 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 b 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-cellgenes relevant to b cell programming and diabetes pathophysiology.