2. Academic Validation
  3. PRMT1 and TDRD3 promote stress granule assembly by rebuilding the protein-RNA interaction network

PRMT1 and TDRD3 promote stress granule assembly by rebuilding the protein-RNA interaction network

  • Int J Biol Macromol. 2024 Aug 2;277(Pt 3):134411. doi: 10.1016/j.ijbiomac.2024.134411.
Mengtong Qin 1,  Weiwei Fan 2,  Linge Li 3,  Tian Xu 2,  Hanyu Zhang 2,  Feng Chen 2,  Jingwen Man 1,  Arnaud John Kombe Kombe 4,  Jiahai Zhang 2,  Yunyu Shi 2,  Xuebiao Yao 2,  Zhenye Yang 5,  Zhonghuai Hou 6,  Ke Ruan 7,  Dan Liu 8
Affiliations

Affiliations

  • 1 MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.
  • 2 MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
  • 3 MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; Department of Chemical Physics, iChEM, University of Science and Technology of China, Hefei 230026, China.
  • 4 Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 5 MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China. Electronic address: zhenye@ustc.edu.cn.
  • 6 MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; Department of Chemical Physics, iChEM, University of Science and Technology of China, Hefei 230026, China. Electronic address: hzhlj@ustc.edu.cn.
  • 7 MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China. Electronic address: kruan@ustc.edu.cn.
  • 8 MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China; The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China. Electronic address: dliu919@ustc.edu.cn.
PMID: 39097054 DOI: 10.1016/j.ijbiomac.2024.134411
Abstract

Stress granules (SGs) are membrane-less organelles (MLOs) or cytosolic compartments formed upon exposure to environmental cell stress-inducing stimuli. SGs are based on ribonucleoprotein complexes from a set of cytoplasmic proteins and mRNAs, blocked in translation due to stress cell-induced polysome disassembly. Post-translational modifications (PTMs) such as methylation, are involved in SG assembly, with the methylation writer PRMT1 and its reader TDRD3 colocalizing to SGs. However, the role of this writer-reader system in SG assembly remains unclear. Here, we found that PRMT1 methylates SG constituent RNA-binding proteins (RBPs) on their RGG motifs. Besides, we report that TDRD3, as a reader of asymmetric dimethylarginines, enhances RNA binding to recruit additional RNAs and RBPs, lowering the percolation threshold and promoting SG assembly. Our study enriches our understanding of the molecular mechanism of SG formation by elucidating the functions of PRMT1 and TDRD3. We anticipate that our study will provide a new perspective for comprehensively understanding the functions of PTMs in liquid-liquid phase separation driven condensate assembly.

Keywords

Asymmetric dimethylarginine; Liquid-liquid phase separation; PRMT1; Stress granule; TDRD3.

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