A long noncoding RNA associated with susceptibility to celiac disease

被引：194

作者：

Castellanos-Rubio, Ainara ^{[1
]}

Fernandez-Jimenez, Nora ^{[2
]}

Kratchmarov, Radomir ^{[1
]}

Luo, Xiaobing ^{[3
]}

Bhagat, Govind ^{[4
,5
]}

Green, Peter H. R. ^{[5
]}

Schneider, Robert ^{[6
]}

Kiledjian, Megerditch ^{[3
]}

Bilbao, Jose Ramon ^{[2
]}

Ghosh, Sankar ^{[1
]}

机构：

[1] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA

[2] Univ Basque Country UPV EHU, BioCruces Res Inst, Dept Genet Phys Anthropol & Anim Physiol, Leioa 48940, Basque Country, Spain

[3] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY 10032 USA

[4] Columbia Univ, Coll Phys & Surg, Dept Med, Ctr Celiac Dis, New York, NY 10032 USA

[5] NYU, Sch Med, Alexandria Ctr Life Sci, New York, NY 10016 USA

[6] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA

来源：

SCIENCE | 2016年 / 352卷 / 6281期

关键词：

GENOME-WIDE ASSOCIATION; MULTIPLE COMMON; REPRESSION; COMPLEXES; VARIANTS; CELL;

D O I：

10.1126/science.aad0467

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recent studies have implicated long noncoding RNAs (lncRNAs) as regulators of many important biological processes. Here we report on the identification and characterization of a lncRNA, lnc13, 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, lnc13 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 lnc13 may contribute to the inflammation seen in this disease. Furthermore, the lnc13 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.

引用

页码：91 / 95

页数：5

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