美国德克萨斯大学西南医学中心Bruce Beutler研究组发现，由剪接体组分Snrnp40的一个不致死的亚效应等位基因所引起的综合性免疫紊乱。相关论文于2019年8月19日在线发表在国际学术期刊《自然—免疫学》杂志上。

研究人员报道了一种小鼠的新型免疫缺陷病，其由Snrnp40的一种不致死亚型突变引起，Snrnp40是一种编码剪接体U5小核核糖核蛋白（snRNP）复合物亚基的必需基因。Snrnp40普遍存在，但在淋巴组织中强烈表达。纯合突变小鼠显示出对鼠巨细胞病毒感染的高度敏感性并出现淋巴发育、稳定性和功能的多种缺陷。造血干细胞分化的缺陷也影响纯合突变体。原发性造血干细胞或T细胞或EL4细胞系中的SNRNP40缺乏增加了数百个信使RNA中剪接错误的频率，主要是内含子遗留。在Snrnp40突变细胞中也观察到与免疫细胞功能相关的蛋白质的改变表达。SNRNP40缺陷的免疫学后果可能是由于对许多不同mRNA分子的加工的累积性中度影响以及关键免疫蛋白表达的二次减少，从而产生综合性免疫疾病。
 

附：英文原文

Title: Syndromic immune disorder caused by a viable hypomorphic allele of spliceosome component Snrnp40

Author: Duanwu Zhang, Tao Yue, Jin Huk Choi, Evan Nair-Gill, Xue Zhong, Kuan-wen Wang, Xiaoming Zhan, Xiaohong Li, Mihwa Choi, Miao Tang, Jiexia Quan, Sara Hildebrand, Eva Marie Y. Moresco, Bruce Beutler 

Issue&Volume: 19 August 2019

Abstract: We report a new immunodeficiency disorder in mice caused by a viable hypomorphic mutation of Snrnp40, an essential gene encoding a subunit of the U5 small nuclear ribonucleoprotein (snRNP) complex of the spliceosome. Snrnp40 is ubiquitous but strongly expressed in lymphoid tissue. Homozygous mutant mice showed hypersusceptibility to infection by murine cytomegalovirus and multiple defects of lymphoid development, stability and function. Cell-intrinsic defects of hematopoietic stem cell differentiation also affected homozygous mutants. SNRNP40 deficiency in primary hematopoietic stem cells or T cells or the EL4 cell line increased the frequency of splicing errors, mostly intron retention, in several hundred messenger RNAs. Altered expression of proteins associated with immune cell function was also observed in Snrnp40-mutant cells. The immunological consequences of SNRNP40 deficiency presumably result from cumulative, moderate effects on processing of many different mRNA molecules and secondary reductions in the expression of critical immune proteins, yielding a syndromic immune disorder.

DOI: https://doi.org/10.1038/s41590-019-0464-4

Source: https://www.nature.com/articles/s41590-019-0464-4