A long noncoding RNA associated with susceptibility to celiac disease.
A long noncoding RNA associated with susceptibility to celiac disease.
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DOI：
10.1126/science.aad0467
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发表时间：
2016-04-01
期刊：
影响因子：
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通讯作者：
Ghosh S
中科院分区：
文献类型：
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作者：
Castellanos-Rubio A;Fernandez-Jimenez N;Kratchmarov R;Luo X;Bhagat G;Green PH;Schneider R;Kiledjian M;Bilbao JR;Ghosh S
最近的研究表明，长链非编码rna （lncRNAs）是许多重要生物过程的调节因子。在这里，我们报道了一种lncRNA， lnc13的鉴定和表征，它含有乳糜泻相关的单倍型阻滞，并在稳态条件下抑制某些炎症基因的表达。Lnc13通过结合hnRNPD调控基因表达，hnRNPD是一个普遍表达的异质核核糖核蛋白（hnRNPs）家族的成员。刺激后，lnc13水平降低，从而使被抑制基因的表达增加。乳糜泻患者的小肠活检样本中Lnc13水平显著降低，这表明Lnc13的下调可能与该疾病中的炎症有关。此外，lnc13疾病相关变体结合hnRNPD的效率低于其野生型对应体，因此有助于解释这些单核苷酸多态性如何导致乳糜泻。
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.