RNA结合蛋白HuR对肠道上皮稳态的转录后调控

Posttranscriptional control of intestinal epithelium homeostasis by RNA-binding protein HuR

哺乳动物的肠上皮组织具备快速和强大的自我更新能力,以适应与肠内容物中众多有害物质和微生物的直接接触。基因的转录后调控是肠上皮组织维持稳态的重要机制之一。RNA结合蛋白HuR在细胞中的主要功能是调节靶向基因转录本的稳定性和翻译,密切参与肠道黏膜病理生理调节。本综述将重点介绍HuR在维持肠上皮完整性方面的生物学作用,尤其是HuR在调节肠上皮细胞更新、肠道黏膜修复以及肠壁通透性方面的最新发现和研究进展;并深入分析HuR与其它RNA结合蛋白以及非编码RNA (包含微小RNA和长链非编码RNA)之间的相互作用在肠上皮稳态调节中的共同作用。随着RNA结合蛋白和非编码RNA研究领域的不断深入,肠上皮组织稳态的转录后调控将为如何在特定病理条件下保护肠上皮的治疗提供新的线索。

The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body and directly interfaces with a wide array of luminal noxious contents and microorganisms.Homeostasis of the intestinal epithelium is preserved through well-controlled mechanisms including posttranscriptional regulation.RNA-binding protein(RBP)HuR regulates the stability and translation of target mRNAs and is intimately involved in many aspects of gut mucosal pathophysiology.Here we highlight the biological roles of HuR in maintaining the integrity of the intestinal epithelium,with particular focus on the emerging evidence of HuR in the regulation of intestinal epithelial renewal,mucosal repair,defense,and gut permeability.We also further analyze the mechanisms through which HuR and its interactions with other RBPs and noncoding RNAs(ncRNAs)such as microRNAs and long ncRNAs modulate the intestinal epithelial homeostasis.With rapidly advancing knowledge of RBPs and ncRNAs,there is growing recognition that posttranscriptional control of the intestinal epithelium homeostasis might be promising therapeutic targets in our efforts to protect the integrity of the intestinal epithelium under critical pathological conditions.