A long noncoding RNA associated with susceptibility to celiac disease

• Published in: Science (American Association for the Advancement of Science) Vol. 352; no. 6281; pp. 91 - 95
• Main Authors: Castellanos-Rubio, Ainara, Fernandez-Jimenez, Nora, Kratchmarov, Radomir, Luo, Xiaobing, Bhagat, Govind, Green, Peter H. R., Schneider, Robert, Kiledjian, Megerditch, Bilbao, Jose Ramon, Ghosh, Sankar
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01-04-2016; The American Association for the Advancement of Science
• Subjects: Animals; Base Sequence; Celiac disease; Celiac Disease - genetics; Celiac Disease - pathology; Down-Regulation; Gene expression; Gene Expression Regulation; Genetic Predisposition to Disease; Haplotypes; Heterogeneous-Nuclear Ribonucleoproteins - genetics; Humans; Inflammation; Inflammation - genetics; Mice; Molecular Sequence Data; Pathogenesis; Polymorphism, Single Nucleotide; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aad0467

Recent studies have implicated long noncoding RNAs (IncRNAs) as regulators of many important biological processes. Here we report on the identification and characterization of a IncRNA, Inc13, that harbors a celiac disease–associated haplotype block and represses expression of certain inflammatory genes under homeostatic conditions. Lnc13 regulates gene expression by binding to hnRNPD, a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). Upon stimulation, Inc13 levels are reduced, thereby allowing increased expression of the repressed genes. Lnc13 levels are significantly decreased in small intestinal biopsy samples from patients with celiac disease, which suggests that down-regulation of Inc13 may contribute to the inflammation seen in this disease. Furthermore, the Inc13 disease-associated variant binds hnRNPD less efficiently than its wild-type counterpart, thus helping to explain how these single-nucleotide polymorphisms contribute to celiac disease.