The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1

Pellizzoni, Livio; Baccon, Jennifer; Charroux, Bernard; Dreyfuss, Gideon

doi:10.1016/s0960-9822(01)00316-5

Cited by 186 publications

(172 citation statements)

References 57 publications

(2 reference statements)

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“…Blocking of the central interaction domain of SMN, the Tudor domain, prevents binding of small nuclear ribonucleoprotein particle core factors (Sm proteins) and abolishes assembly of small nuclear ribonucleoprotein. Deletion of 27 residues from the N terminus of SMN leads to inhibition of small nuclear ribonucleoprotein assembly, splicing, and transcription (51,52).…”

Section: Discussionmentioning

confidence: 99%

Differential Intranuclear Localization of Fibroblast Growth Factor-2 Isoforms and Specific Interaction with the Survival of Motoneuron Protein

Claus¹,

Döring²,

Gringel³

et al. 2003

Journal of Biological Chemistry

119

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Fibroblast growth factor 2 (FGF-2) is an important modulator of cell growth and differentiation and a neurotrophic factor. FGF-2 occurs in isoforms, at a low molecular weight of 18,000 and at least two high molecular weight forms (21,000 and 23,000), representing alternative translation products from a single mRNA. In addition to its role as an extracellular ligand, FGF-2 localizes to the nuclei of cells. Here we show differential localization of the 18-and 23-kDa isoforms in the nuclei of rat Schwann cells. Whereas the 18-kDa isoform was found in the nucleoli, nucleoplasm, and Cajal bodies, the 23-kDa isoform localized in a punctuate pattern and associates with mitotic chromosomes suggesting different functional roles of the isoforms. Moreover, we show here that the 23-kDa FGF-2 isoform co-immunoprecipitates specifically with the survival of motor neuron protein (SMN). SMN is an assembly and recycling factor of the splicing machinery and locates to the cytoplasm, the nucleoplasm, and nuclear gems, where it co-localizes with 23-kDa FGF-2. Patients with spinal muscular atrophy suffer from fatal degeneration of motoneurons because of mutations and deletions of the gene for the SMN protein.A number of mitogenic growth factors, growth-regulatory proteins, and growth factor receptors have been reported to be localized in the cell nucleus and its substructures: e.g. plateletderived growth factor, fibroblast growth factor-1 (FGF-1), 1 FGF-2, and ciliary neurotrophic factor (1, 2). The data show that nuclear localization is a general phenomenon for some growth factors, suggesting nuclear functions independent of the function as extracellular factors.FGF-2 is a member of the FGF family, which has been shown to mediate a variety of biological processes during development and in the adult organism, including mitogenesis, angiogenesis, chemotaxis, mesoderm induction, and differentiation of various mesoderm-and neuroectoderm-derived cells. FGF-2 as an extracellular ligand is able to bind to high affinity tyrosine transmembrane receptors (FGF receptors, FGFR). FGF-2 has been shown to bind to all four known FGFR, however, with distinct affinities (3).FGF-2 exists in protein isoforms translated from a common messenger RNA by alternative use of AUG (18,000 isoform) and CUG (high molecular weight isoforms 21,000 and 23,000) start codons. The isoforms exert different biological effects when overexpressed in different cell types. Specific effects seen by the 23-kDa isoform but not the 18-kDa isoform after overexpression are reduced spreading of pancreatic cancer cells (4), the ability of NIH 3T3 cells to grow in low serum medium (5), increased radioresistance in HeLa cells (6), growing in serumfree medium of rat AR4 -2J cells (7), and differential effects on binucleation and nuclear morphology of neonatal rat cardiac myocytes (8). We have previously shown that in PC12 cells and rat immortalized Schwann cells, cell growth and morphology are altered after transfection with constructs coding for 18-and 23-kDa FGF-2, respectively (9, 1...

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Section: Discussionmentioning

confidence: 99%

Differential Intranuclear Localization of Fibroblast Growth Factor-2 Isoforms and Specific Interaction with the Survival of Motoneuron Protein

Claus¹,

Döring²,

Gringel³

et al. 2003

Journal of Biological Chemistry

119

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“…In vitro binding assays performed with full-length and truncated forms of the protein showed that SMN interacts directly with both fibrillarin and GAR1 and that the interactions are mediated by the RG-rich domains of fibrillarin and GAR1. Co-immunoprecipitation experiments demonstrated that the SMN complex interacts with fibrillarin and GAR1 in vivo in human cells (Pellizzoni et al 2001a). Furthermore, overexpression of a dominant-negative mutant of SMN, SMNΔN27, causes a massive reorganization of snoRNPs, pointing again to a functional interaction between snoRNPs and the SMN complex in vivo.…”

Section: A Role For the Smn Complex In The Biogenesis Of Other Rnpsmentioning

confidence: 96%

“…SMN also binds directly to fibrillarin and GAR1, constituents of box C/D and box H/ACA small nucleolar RNPs (snoRNPs), respectively (Jones et al 2001;Pellizzoni et al 2001a). In vitro binding assays performed with full-length and truncated forms of the protein showed that SMN interacts directly with both fibrillarin and GAR1 and that the interactions are mediated by the RG-rich domains of fibrillarin and GAR1.…”

Section: A Role For the Smn Complex In The Biogenesis Of Other Rnpsmentioning

confidence: 99%

The SMN Complex: An Assembly Machine for RNPs

Battle¹,

Kasim²,

Yong³

et al. 2006

Cold Spring Harbor Symposia on Quantitative Biology

167

156

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“…Previous studies have provided evidence that the SMN complex functions in the assembly of spliceosomal snRNPs, pre-mRNA splicing, and transcription (16, 20, 24 -26). The SMN complex may also play a role in the metabolism of snoRNPs involved in processing and modification of ribosomal RNA (18,19).Although the molecular mechanisms of SMN function are not yet known, these findings have led to the proposal that the SMN complex is a macromolecular machine, which functions in the assembly and function of several RNP complexes (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Understanding the function of the SMN complex at the molecular level is necessary to uncover the defect responsible for SMA.…”

mentioning

confidence: 99%

Purification of Native Survival of Motor Neurons Complexes and Identification of Gemin6 as a Novel Component

Pellizzoni

Baccon

Rappsilber

et al. 2002

Journal of Biological Chemistry

Self Cite

119

133

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The survival of motor neurons (SMN) protein, the product of the gene responsible for the motor neuron degenerative disease spinal muscular atrophy (SMA), is part of a large macromolecular complex. The SMN complex is localized in both the cytoplasm and the nucleus and contains SMN, Gemin2, Gemin3, Gemin4, Gemin5, and a few not yet identified proteins. The SMN complex plays a key role in the biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and other ribonucleoprotein particles. As a step toward the complete characterization of the components of the SMN complex, we generated stable cell lines that express FLAG-tagged SMN or Gemin2 under the control of a tetracycline-inducible promoter. Native SMN complexes of identical protein composition to those isolated by immunoprecipitation with anti-SMN antibodies were purified by affinity chromatography from extracts of both cell lines. Here we report the identification by mass spectrometry of a novel protein component of the SMN complex termed Gemin6. Co-immunoprecipitation, immunolocalization, and in vitro binding experiments demonstrate that Gemin6 is a component of the SMN complex that localizes to gems and interacts with several Sm proteins of the spliceosomal snRNPs. Spinal muscular atrophy (SMA)1 is an autosomal recessive disease characterized by degeneration of motor neurons of the spinal cord resulting in muscular atrophy (1). SMA is the most common genetic cause of infant mortality and the second most frequent lethal autosomal recessive disease after cystic fibrosis. Deletions or mutations in the survival of motor neurons (SMN1) gene, the SMA-causing gene, are detected in over 95% of SMA patients (2). SMN is essential for viability in all organisms and cell types tested, including humans, mice, chicken DT40 cells, Drosophila melanogaster, Caenorhabditis elegans, and Schizosaccharomyces pombe (3-9).SMN associates with Gemin2 (10), Gemin3 (11), Gemin4 (12), and Gemin5 (13) and a few not yet identified components to form a large multiprotein complex. The SMN complex is found both in the cytoplasm and in the nucleus, where it is concentrated in gems, nuclear bodies similar in size and number to Cajal (coiled) bodies and often associated with them (14). In addition to the integral components of the SMN complex described above, several proteins have been identified that directly interact with SMN and/or the Gemins. These include the spliceosomal snRNP Sm and Lsm proteins (10, 15-17), the snoRNP proteins fibrillarin and GAR1 (18, 19), RNA helicase A (20), hnRNP Q (21), and coilin (22). A strong correlation has emerged between a defect of SMN interaction with these proteins and the SMA phenotype, because SMN, but not SMN mutants found in SMA patients, interact directly with these proteins (15)(16)(17)(18)(19)(20)(21)(22). A common feature of these proteins is the presence of arginine-and glycine-rich (RG) domains that are necessary for their direct interaction with SMN (17-22). Specific arginine residues of these domains are di-methylated in vivo, and t...

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The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1

Cited by 186 publications

References 57 publications

Differential Intranuclear Localization of Fibroblast Growth Factor-2 Isoforms and Specific Interaction with the Survival of Motoneuron Protein

Differential Intranuclear Localization of Fibroblast Growth Factor-2 Isoforms and Specific Interaction with the Survival of Motoneuron Protein

The SMN Complex: An Assembly Machine for RNPs

Purification of Native Survival of Motor Neurons Complexes and Identification of Gemin6 as a Novel Component

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