近日，美国哈佛大学Ramnik J. Xavier等研究人员合作发现，QRICH1通过蛋白质稳态的转录调控来决定内质网应激的结果。2021年1月1日出版的《科学》杂志发表了这项成果。

据研究人员介绍，组织稳态在多种炎性病理中均受到干扰。这些变化会引起内质网（ER）压力、蛋白质错误折叠和细胞死亡。内质网应激会触发未折叠蛋白反应（UPR），从而促进内质网蛋白稳态和细胞存活或触发程序性细胞死亡。

研究人员利用单细胞RNA测序来定义了与小鼠肠上皮中的适应性UPR与最终UPR相关的动态转录状态。研究人员将这些转录程序与基因组规模的CRISPR筛选相结合，从而在功能上剖析了UPR途径。研究人员发现，QRICH1是UPR中PERK-eIF2α信号轴的关键效应因子。QRICH1控制与转录和分泌网络相关的转录程序，这些转录和分泌网络在炎症性病理中被上调。因此，QRICH1决定了细胞对病理性ER应激的反应。

附：英文原文

Title: QRICH1 dictates the outcome of ER stress through transcriptional control of proteostasis

Author: Kwontae You, Lingfei Wang, Chih-Hung Chou, Kai Liu, Toru Nakata, Alok Jaiswal, Junmei Yao, Ariel Lefkovith, Abdifatah Omar, Jacqueline G. Perrigoue, Jennifer E. Towne, Aviv Regev, Daniel B. Graham, Ramnik J. Xavier

Issue&Volume: 2021/01/01

Abstract: Tissue homeostasis is perturbed in a diversity of inflammatory pathologies. These changes can elicit endoplasmic reticulum (ER) stress, protein misfolding, and cell death. ER stress triggers the unfolded protein response (UPR), which can promote recovery of ER proteostasis and cell survival or trigger programmed cell death. Here, we leveraged single-cell RNA sequencing to define dynamic transcriptional states associated with the adaptive versus terminal UPR in the mouse intestinal epithelium. We integrated these transcriptional programs with genome-scale CRISPR screening to dissect the UPR pathway functionally. We identified QRICH1 as a key effector of the PERK-eIF2α axis of the UPR. QRICH1 controlled a transcriptional program associated with translation and secretory networks that were specifically up-regulated in inflammatory pathologies. Thus, QRICH1 dictates cell fate in response to pathological ER stress.

DOI: 10.1126/science.abb6896

Source: https://science.sciencemag.org/content/371/6524/eabb6896