RNA-Binding Proteins; Nerve Tissue Proteins; SMN Complex Proteins; PRMT1 protein, human; Protein-Arginine N-Methyltransferases; Repressor Proteins; Humans; Nerve Tissue Proteins/metabolism; Cell Nucleolus/metabolism; Motor Neurons/metabolism; SMN Complex Proteins/metabolism; Coiled Bodies/metabolism; Protein-Arginine N-Methyltransferases/metabolism; Repressor Proteins/metabolism; RNA-Binding Proteins/metabolism; Muscular Atrophy, Spinal/genetics; Muscular Atrophy, Spinal/metabolism; Cell Nucleolus; Coiled Bodies; Motor Neurons; Muscular Atrophy, Spinal; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all); General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
Abstract :
[en] Spinal muscular atrophy is an autosomal recessive neuromuscular disease caused by mutations in the multifunctional protein Survival of Motor Neuron, or SMN. Within the nucleus, SMN localizes to Cajal bodies, which are associated with nucleoli, nuclear organelles dedicated to the first steps of ribosome biogenesis. The highly organized structure of the nucleolus can be dynamically altered by genotoxic agents. RNAP1, Fibrillarin, and nucleolar DNA are exported to the periphery of the nucleolus after genotoxic stress and, once DNA repair is fully completed, the organization of the nucleolus is restored. We find that SMN is required for the restoration of the nucleolar structure after genotoxic stress. During DNA repair, SMN shuttles from the Cajal bodies to the nucleolus. This shuttling is important for nucleolar homeostasis and relies on the presence of Coilin and the activity of PRMT1.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Musawi, Shaqraa; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France ; Department of Medical Laboratories Technology, College of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia
Donnio, Lise-Marie; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France. lise-marie.donnio@univ-lyon1.fr
Zhao, Zehui; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Magnani, Charlène; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Rassinoux, Phoebe; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Binda, Olivier; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France ; Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, K1H 8M5, Ontario, Canada
Huang, Jianbo ; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Jacquier, Arnaud ; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Coudert, Laurent; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Lomonte, Patrick ; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Martinat, Cécile ; INSERM/UEPS UMR 861, Paris Saclay Université, I-STEM, 91100, Corbeil-Essonnes, France
Schaeffer, Laurent ; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Mottet, Denis ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Côté, Jocelyn ; Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, K1H 8M5, Ontario, Canada
Mari, Pierre-Olivier; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France
Giglia-Mari, Giuseppina ; Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM), CNRS UMR 5261, INSERM U1315, Université Claude Bernard Lyon 1, 68008, Lyon, France. ambra.mari@univ-lyon1.fr
AFM-Téléthon [FR] CSC - China Scholarship Council [CN]
Funding text :
Dedicated to the mothers and fathers of children affected with SMA. We would like to thank Laura Trinkle-Mulcahy for the generous gift of the mCherry-N1. For access to the confocal microscope, we acknowledge the contribution of the imaging facility CIQLE [https://ciqle.univ-lyon1.fr] (Centre d’imagerie Quantitative Lyon-Est - SFR Santé Lyon-Est, UAR3453 CNRS, US7 INSERM, UCBL), a member of LyMIC (Lyon Multiscale Imaging Center). This work was supported by AFM-Téléthon (MyoNeurALP 1 and 2) and by Institut National du Cancer (InCa, PLBIO19-126). S.M. was funded by Jazan university, Jazan, Saudi Arabia. L.M.D. is funded by AFM-Téléthon (MyoNeurALP 2). Z.Z. and J.H. are funded by China Scholarship Council (CSC). P.L. and O.B. are funded by an AFM-Téléthon grant (MyoNeurALP) and by the Joint Collaborative Research Program between the Centre for Neuromuscular Disease (University of Ottawa) and Institut NeuroMyoGène (INMG - Claude Bernard Université Lyon 1). J.C. is funded by a Canadian Institutes of Health Research (CIHR) grant (MOP 123381) and CureSMA Canada. D.M. is a FNRS Research Associate and is funded by grants from the FNRS – Belgium, Fonds Léon Frédéricq (FLF) and Fonds Spéciaux de la Recherche de l’Université de Liège (ULiege).Dedicated to the mothers and fathers of children affected with SMA. We would like to thank Laura Trinkle-Mulcahy for the generous gift of the mCherry-N1. For access to the confocal microscope, we acknowledge the contribution of the imaging facility CIQLE [ https://ciqle.univ-lyon1.fr ] (Centre d’imagerie Quantitative Lyon-Est - SFR Santé Lyon-Est, UAR3453 CNRS, US7 INSERM, UCBL), a member of LyMIC (Lyon Multiscale Imaging Center). This work was supported by AFM-Téléthon (MyoNeurALP 1 and 2) and by Institut National du Cancer (InCa, PLBIO19-126). S.M. was funded by Jazan university, Jazan, Saudi Arabia. L.M.D. is funded by AFM-Téléthon (MyoNeurALP 2). Z.Z. and J.H. are funded by China Scholarship Council (CSC). P.L. and O.B. are funded by an AFM-Téléthon grant (MyoNeurALP) and by the Joint Collaborative Research Program between the Centre for Neuromuscular Disease (University of Ottawa) and Institut NeuroMyoGène (INMG - Claude Bernard Université Lyon 1). J.C. is funded by a Canadian Institutes of Health Research (CIHR) grant (MOP 123381) and CureSMA Canada. D.M. is a FNRS Research Associate and is funded by grants from the FNRS – Belgium, Fonds Léon Frédéricq (FLF) and Fonds Spéciaux de la Recherche de l’Université de Liège (ULiege).
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