文献类型： 外文期刊

作者： Lu, Tong ¹ ; Ma, Pengcheng ³ ; Fang, Hailing ¹ ; Chen, Aijun ¹ ; Xu, Jianlin ³ ; Kuang, Xi ¹ ; Wang, Mingyu ⁶ ; Su, Ling ¹ ; Wang, Sen ⁶ ; Zhang, Yizhuang ¹ ; Wang, Jiasheng ¹ ; Yang, Boya ¹ ; Shi, De-Li ⁷ ; Zhou, Yong ⁹ ; Gong, Qianqian ¹ ; Liu, Xiangguo ¹ ; Mao, Bingyu ³ ; Shao, Ming ¹ ;

作者机构： 1.Shandong Univ, Cheeloo Coll Med, Shandong Prov Key Lab Anim Cell & Dev Biol, Sch Life Sci, Qingdao 266237, Peoples R China

2.Shandong Univ, Qilu Hosp Qingdao, Cheeloo Coll Med, Qingdao 266237, Peoples R China

3.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Evolut & Anim Models, Kunming 650201, Peoples R China

4.Chinese Acad Sci, Kunming Inst Zool, Natl Resource Ctr Nonhuman Primates, Kunming 650107, Yunnan, Peoples R China

5.Chinese Acad Sci, Kunming Inst Zool, Natl Res Facil Phenotyp & Genet Anal Model Anim Pr, Kunming 650107, Yunnan, Peoples R China

6.Inst Microbial Technol, State Key Lab Microbial Technol, Qingdao 266237, Peoples R China

7.Sorbonne Univ, Inst Biol Paris Seine IBPS, UMR 8263, INSERM,U1345,CNRS,Dev Adaptat & Ageing, Paris, France

8.Ocean Univ China, Coll Marine Life Sci, Fang Zongxi Ctr, Key Lab Marine Genet & Breeding, Qingdao, Peoples R China

9.Chinese Acad Fishery Sci, Yangtze River Fisheries Res Inst, Wuhan 430223, Peoples R China

10.Shandong Univ, Key Lab Expt Teratol, Minist Educ, Qingdao 266237, Peoples R China

11.Shandong Univ, Yuanchen Joint Biomed Technol Lab, Qingdao 266237, Peoples R China

期刊名称：MOLECULAR CELL （ 影响因子：16.6； 五年影响因子：17.7 ）

ISSN： 1097-2765

年卷期： 2025 年 85 卷 10 期

页码：

收录情况： SCI

摘要： Double-stranded RNAs (dsRNAs), known as conserved pathogen-associated molecular patterns, activate the integrated stress response via interferon-induced protein kinase R (PKR), leading to global translation inhibition. However, the interferon system is inactive in pluripotent cells, leaving the mechanisms of dsRNA sensing and translational control unclear. In this study, we utilized early zebrafish embryos as a model of pluripotent cells and discovered a PKR-independent blockage of translation initiation by dsRNA stimulation. Prkra dimer was identified as the genuine dsRNA sensor. Upon dsRNA binding, the dimerized dsRNA-binding domain 3 of Prkra becomes activated to sequester the eIF2 complexes from the translation machinery, inhibiting global protein synthesis. This distinctive embryonic stress response restricts RNA virus replication in zebrafish embryos, is conserved in mouse embryonic stem cells, and compensates PKR function in differentiated cells. Therefore, the Prkra-mediated dsRNA sensing and translation control may serve as a common strategy for cells to adapt to environmental stresses.