Balancing RNA processing and innate immune response: Possible roles for SMN condensates in snRNP biogenesis

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 3; p. 130764
• Main Authors: Maita, Hiroshi, Nakagawa, Shinichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2025
• Subjects: Animals; biogenesis; Biomolecular Condensates - metabolism; Cajal body; Coilin; cytoplasm; domain; Humans; Immunity, Innate; inflammation; innate immunity; Intrinsically disordered region; mammals; metabolism; muscular atrophy; Muscular Atrophy, Spinal - genetics; Muscular Atrophy, Spinal - immunology; Muscular Atrophy, Spinal - metabolism; ribonucleoproteins; Ribonucleoproteins, Small Nuclear - genetics; Ribonucleoproteins, Small Nuclear - immunology; Ribonucleoproteins, Small Nuclear - metabolism; RNA; RNA Processing, Post-Transcriptional; SMN; SMN Complex Proteins - genetics; SMN Complex Proteins - metabolism; Symmetrical arginine dimethylation; therapeutics; Tudor domain; U-body; Tudor domain; Symmetrical arginine dimethylation; SMN; Coilin; Cajal body; Intrinsically disordered region; U-body
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2025.130764

Biomolecular condensates like U-bodies are specialized cellular structures formed through multivalent interactions among intrinsically disordered regions. U-bodies sequester small nuclear ribonucleoprotein complexes (snRNPs) in the cytoplasm, and their formation in mammalian cells depends on stress conditions. Because of their location adjacent to P-bodies, U-bodies have been considered potential sites for snRNP storage or turnover. SMN, a chaperone for snRNP biogenesis, forms condensates through its Tudor domain. In fly models, defects in SMN trigger innate immune responses similar to those observed with excess cytoplasmic snRNA during viral infection in mammalian cells. Additionally, spinal muscular atrophy (SMA), caused by SMN deficiency, is associated with inflammation. Therefore, SMN may help prevent innate immune aberrant activation due to defective snRNP biogenesis by forming U-bodies to sequester these molecules. Further studies on U-body functions may provide therapeutic insights for diseases related to RNA metabolism. •Excessive snRNA or defective snRNA triggers activation of innate immune signaling.•Processing-defective snRNA accumulates in U-bodies, cytoplasmic foci overlapping with P-bodies.•Mutant animals lacking functional SMN exhibit innate immune activation and show defects in U-body formation.•U-bodies may modulate the innate immune response.