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

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  • Author(s): Wang L;Wang L;Wang L; Li P; Li P; Li P
  • Source:
    Cell reports [Cell Rep] 2024 Aug 27; Vol. 43 (8), pp. 114537. Date of Electronic Publication: 2024 Jul 24.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Cambridge, MA] : Cell Press, c 2012-
    • Subject Terms:
      RNA-Binding Protein FUS*/metabolism ; Arginine*/metabolism ; Cytoplasmic Granules*/metabolism; Methylation ; Humans ; Animals ; Mice ; Neurons/metabolism ; Axons/metabolism ; Survival of Motor Neuron 1 Protein/metabolism ; Survival of Motor Neuron 1 Protein/genetics ; Phase Separation
    • 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.
      Competing Interests: Declaration of interests The authors declare no competing interests.
      (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: CP: Cell biology; CP: Molecular biology
    • Accession Number:
      0 (RNA-Binding Protein FUS)
      94ZLA3W45F (Arginine)
      0 (FUS protein, human)
      0 (Survival of Motor Neuron 1 Protein)
    • Publication Date:
      Date Created: 20240725 Date Completed: 20240830 Latest Revision: 20240831
    • Publication Date:
      20240831
    • Accession Number:
      10.1016/j.celrep.2024.114537
    • Accession Number:
      39052476