Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China; Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China; Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
FEBS J. 2015 Mar;282(5):874-90. doi: 10.1111/febs.13186. Epub 2015 Jan 26.
Stress granules (SGs) and processing bodies (PBs) comprise the main types of cytoplasmic RNA foci during stress. Our previous data indicate that knockdown of human Tudor staphylococcal nuclease (Tudor-SN) affects the aggregation of SGs. However, the precise molecular mechanism has not been determined fully. In the present study, we demonstrate that Tudor-SN binds and colocalizes with many core components of SGs, such as poly(A)(+) mRNA binding protein 1, T-cell internal antigen-1-related protein and poly(A)(+) mRNA, and SG/PB sharing proteins Argonaute 1/2, but not PB core proteins, such as decapping enzyme 1 a/b, confirming that Tudor-SN is an SG-specific protein. We also demonstrate that the Tudor-SN granule actively communicates with the nuclear and cytosolic pool under stress conditions. Tudor-SN can regulate the aggregation dynamics of poly(A)(+) mRNA-containing SGs and selectively stabilize the SG-associated mRNA during cellular stress.
应激颗粒 (SGs) 和处理体 (PBs) 在应激过程中构成了细胞质 RNA 焦点的主要类型。我们之前的数据表明，人 Tudor 葡萄球菌核酸酶 (Tudor-SN) 的敲低会影响 SGs 的聚集。然而，精确的分子机制尚未完全确定。在本研究中，我们证明 Tudor-SN 与 SGs 的许多核心成分结合并共定位，如 poly(A)(+) mRNA 结合蛋白 1、T 细胞内抗原-1 相关蛋白和 poly(A)(+) mRNA，以及 SG/PB 共享蛋白 Argonaute 1/2，但不与 PB 核心蛋白如脱帽酶 1a/b 结合，证实 Tudor-SN 是一种 SG 特异性蛋白。我们还证明，在应激条件下，Tudor-SN 颗粒与核和胞质池之间能够进行有效通讯。Tudor-SN 可以调节富含 poly(A)(+) mRNA 的 SGs 的聚集动力学，并在细胞应激期间选择性地稳定与 SG 相关的 mRNA。
