The Spinal Muscular Atrophy Disease Gene Product, SMN, and Its Associated Protein SIP1 Are in a Complex with Spliceosomal snRNP Proteins

Liu, Qing; Fischer, Utz; Wang, Fan; Dreyfuss, Gideon

doi:10.1016/s0092-8674(00)80367-0

Cited by 582 publications

(622 citation statements)

References 46 publications

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“…63 Subsequently, SMN was shown to directly interact with these proteins. 45,[66][67][68] Furthermore, co-fractionation studies with HeLa cytosolic extracts demonstrated that SMN, SPN1 and importin b were present in a novel, pre-import RNP complex. 45,62 Along with several other hints in the literature, 32,44,69 these findings suggested that SMN functions to bridge the gap between the Sm core and the import machinery.…”

Section: Smn and Cytoplasmic Snrnp Assemblymentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body.

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Section: Smn and Cytoplasmic Snrnp Assemblymentioning

confidence: 99%

SMN - A chaperone for nuclear RNP social occasions?

2016

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“…After several washes, cells were mounted in Vectashield medium (Vector Laboratories). Primary antibodies used were anti-coilin 204.10 rabbit serum (Bohmann et al 1995), anti-SMN monoclonal antibody (mAb) (Transduction Laboratories), anti-SMN 2B1 mAb (Liu and Dreyfuss 1996), anti-Gemin2/SIP1 E17 mAb (Liu et al 1997), anti-Sm C45 human serum, anti-U2B" 4G3 mAb, and anti-Nopp 140 rabbit serum RF12 (Meier and Blobel 1992). Cell samples were examined using a Zeiss 63× NA 1.4 PlanApo objective.…”

Section: Fluorescence Microscopy and Immunostainingmentioning

confidence: 99%

Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

et al. 2004

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Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells are a good model system for studying the peripheral nervous system and the outgrowth of neurites. In addition to the dramatic changes observed in the cytoplasm, neuronal differentiation is also accompanied by striking changes in nuclear morphology. The large and sustained increase in nuclear transcription during neuronal differentiation requires synthesis of a large number of factors involved in pre-mRNA processing. We show that the number and composition of the nuclear subdomains called Cajal bodies and gems changes during the course of N-ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies found in undifferentiated cells are largely devoid of the survival of motor neurons (SMN) protein product. As cells shift to a differentiated state, SMN is not only globally upregulated, but is progressively recruited to Cajal bodies. Additional SMN foci (also known as Gemini bodies, gems) can also be detected. Using dual-immunogold labeling electron microscopy and mouse embryonic fibroblasts lacking the coilin protein, we show that gems clearly represent a distinct category of nuclear body.

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“…SMA is caused by mutations in the human Survival of motor neuron-1 (Smn1) gene (15). The SMN protein is nuclear Gemin-1, which functions as part of the SMN complex in the assembly of small nuclear ribonucleoproteins that form the spliceosome (16). SMN is thus critical for the splicing of pre-mRNAs; however, it remains contentious if this defective splicing function is causative in the disease (16).…”

Section: Introductionmentioning

confidence: 99%

DNA Damage Response and DNA Repair in Skeletal Myocytes From a Mouse Model of Spinal Muscular Atrophy

Fayzullina

Martin

2016

J Neuropathol Exp Neurol

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We studied DNA damage response (DDR) and DNA repair capacities of skeletal muscle cells from a mouse model of infantile spinal muscular atrophy (SMA) caused by loss-of-function mutation of survival of motor neuron (Smn). Primary myocyte cultures derived from skeletal muscle satellite cells of neonatal control and mutant SMN mice had similar myotube length, myonuclei, satellite cell marker Pax7 and differentiated myotube marker myosin, and acetylcholine receptor clustering. DNA damage was induced in differentiated skeletal myotubes by c-irradiation, etoposide, and methyl methanesulfonate (MMS). Unexposed control and SMA myotubes had stable genome integrity. After c-irradiation and etoposide, myotubes repaired most DNA damage equally. Control and mutant myotubes exposed to MMS exhibited equivalent DNA damage without repair. Control and SMA myotube nuclei contained DDR proteins phosphop53 and phospho-H2AX foci that, with DNA damage, dispersed and then re-formed similarly after recovery. We conclude that mouse primary satellite cell-derived myotubes effectively respond to and repair DNA strand-breaks, while DNA alkylation repair is underrepresented. Morphological differentiation, genome stability, genome sensor, and DNA strand-break repair potential are preserved in mouse SMA myocytes; thus, reduced SMN does not interfere with myocyte differentiation, genome integrity, and DNA repair, and faulty DNA repair is unlikely pathogenic in SMA.

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The Spinal Muscular Atrophy Disease Gene Product, SMN, and Its Associated Protein SIP1 Are in a Complex with Spliceosomal snRNP Proteins

Cited by 582 publications

References 46 publications

SMN - A chaperone for nuclear RNP social occasions?

SMN - A chaperone for nuclear RNP social occasions?

Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

DNA Damage Response and DNA Repair in Skeletal Myocytes From a Mouse Model of Spinal Muscular Atrophy

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