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  2. Arginine methylation-enabled FUS phase separation with SMN contributes to neuronal granule formation

Arginine methylation-enabled FUS phase separation with SMN contributes to neuronal granule formation

  • Cell Rep. 2024 Aug 27;43(8):114537. doi: 10.1016/j.celrep.2024.114537.
Lingyao Wang 1 Pilong Li 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.
  • 2 State Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China. Electronic address: pilongli@mail.tsinghua.edu.cn.
Abstract

Various ribonucleoprotein complexes (RNPs) often function in the form of membraneless organelles derived from multivalence-driven liquid-liquid phase separation (LLPS). Post-translational modifications, such as phosphorylation and arginine methylation, govern the assembly and disassembly of membraneless organelles. This study reveals that asymmetric dimethylation of arginine can create extra binding sites for multivalent Tudor domain-containing proteins like survival of motor neuron (SMN) protein, thereby lowering the threshold for LLPS of RNPs, such as fused in sarcoma (FUS). Accordingly, FUS hypomethylation or knockdown of SMN disrupts the formation and transport of neuronal granules in axons. Wild-type SMN, but not the spinal muscular atrophy-associated form of SMN, SMN-Δ7, rescues neuronal defects due to SMN knockdown. Importantly, a fusion of SMN-Δ7 to an exogenous oligomeric protein is sufficient to rescue axon length defects caused by SMN knockdown. Our findings highlight the significant role of arginine methylation-enabled multivalent interactions in LLPS and suggest their potential impact on various aspects of neuronal activities in neurodegenerative diseases.

Keywords

CP: Cell biology; CP: Molecular biology.

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