This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Kolb, S. J. Articles by Dreyfuss, G. Search for Related Content PubMed PubMed Citation Articles by Kolb, S. J. Articles by Dreyfuss, G. Social Bookmarking                         What's this?

Molecular Functions of the SMN Complex

Howard Hughes Medical Institute and the Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia

Daniel J. Battle, PhD

Howard Hughes Medical Institute and the Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia

Gideon Dreyfuss, PhD

Howard Hughes Medical Institute and the Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, gdreyfuss{at}hhmi.upenn.edu

The SMN complex is essential for the biogenesis of spliceosomal small nuclear ribonucleoproteins and likely functions in the assembly, metabolism, and transport of a diverse number of other ribonucleoproteins. Specifically, the SMN complex assembles 7 Sm proteins into a core structure around a highly conserved sequence of ribonucleic acid (RNA) found in small nuclear RNAs. The complex recognizes specific sequences and structural features of small nuclear RNAs and Sm proteins and assembles small nuclear ribonucleoproteins in a stepwise fashion. In addition to the SMN protein, the SMN complex contains 7 additional proteins known as Gemin2-8, each likely to play a role in ribonucleoprotein biogenesis. This review focuses on the current understanding of the mechanism of the role of the SMN complex in small nuclear ribonucleoprotein assembly and considers the relationship of this function to spinal muscular atrophy.

Key Words: spinal muscular atrophy • ribonucleoproteins • Gemin2-8

References

• Monani UR Spinal muscular atrophy: a deficiency in a ubiquitous protein: a motor neuron-specific disease. Neuron. 2005; 48:885-896.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Lefebvre S., Burglen L., Reboullet S., et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80:155-165.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Meister G., Eggert C., Fischer U. SMN-mediated assembly of RNPs: a complex story. Trends Cell Biol. 2002;12:472-478.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Paushkin S., Gubitz AK, Massenet S., Dreyfuss G. The SMN complex, an assemblyosome of ribonucleoproteins. Curr Opin Cell Biol. 2002;14:305-312.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pellizzoni L. Chaperoning ribonucleoprotein biogenesis in health and disease. EMBO Rep. 2007;8:340-345.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Battle DJ, Kasim M., Yong J., et al. The SMN complex: an assembly machine for RNPs. Cold Spring Harb Symp Quant Biol. 2006;71:313-320.[CrossRef][Medline] [Order article via Infotrieve]
• Baccon J., Pellizzoni L., Rappsilber J., Mann M., Dreyfuss G. Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex. J Biol Chem. 2002; 277:31957-31962.[Abstract/Free Full Text]
• Charroux B., Pellizzoni L., Perkinson RA, Shevchenko A., Mann M., Dreyfuss G. Gemin3: a novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems. J Cell Biol. 1999;147:1181-1194.[Abstract/Free Full Text]
• Charroux B., Pellizzoni L., Perkinson RA, et al. Gemin4: a novel component of the SMN complex that is found in both gems and nucleoli. J Cell Biol. 2000;148:1177-1186.[Abstract/Free Full Text]
• Gubitz AK, Mourelatos Z., Abel L., Rappsilber J., Mann M., Dreyfuss G. Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. J Biol Chem. 2002; 277:5631-5636.[Abstract/Free Full Text]
• Liu Q., Dreyfuss G. A novel nuclear structure containing the survival of motor neurons protein. EMBO J. 1996;15:3555-3565.[Web of Science][Medline] [Order article via Infotrieve]
• Liu Q., Fischer U., Wang F., Dreyfuss G. The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell. 1997; 90:1013-1021.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pellizzoni L., Baccon J., Rappsilber J., Mann M., Dreyfuss G. Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component. J Biol Chem. 2002;277:7540-7545.[Abstract/Free Full Text]
• Carissimi C., Saieva L., Baccon J., et al. Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly. J Biol Chem. 2006; 281:8126-8134.[Abstract/Free Full Text]
• Pellizzoni L., Yong J., Dreyfuss G. Essential role for the SMN complex in the specificity of snRNP assembly. Science. 2002; 298:1775-1779.[Abstract/Free Full Text]
• Yong J., Pellizzoni L., Dreyfuss G. Sequence-specific interaction of U1 snRNA with the SMN complex. EMBO J. 2002;21:1188-1196.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Yong J., Wan L., Dreyfuss G. Why do cells need an assembly machine for RNA-protein complexes? Trends Cell Biol. 2004; 14:226-232.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Friesen WJ, Dreyfuss G. Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN). J Biol Chem. 2000;275: 26370-26375.[Abstract/Free Full Text]
• Buhler D., Raker V., Luhrmann R., Fischer U. Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: implications for spinal muscular atrophy. Hum Mol Genet. 1999; 8:2351-2357.[Abstract/Free Full Text]
• Gubitz AK, Feng W., Dreyfuss G. The SMN complex. Exp Cell Res. 2004;296:51-56.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Jones KW, Gorzynski K., Hales CM, et al. Direct interaction of the spinal muscular atrophy disease protein SMN with the small nucleolar RNA-associated protein fibrillarin. J Biol Chem. 2001; 276:38645-38651.[Abstract/Free Full Text]
• Meister G., Buhler D., Laggerbauer B., Zobawa M., Lottspeich F., Fischer U. Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins. Hum Mol Genet. 2000;9:1977-1986.[Abstract/Free Full Text]
• Mourelatos Z., Abel L., Yong J., Kataoka N., Dreyfuss G. SMN interacts with a novel family of hnRNP and spliceosomal proteins. EMBO J. 2001;20:5443-5452.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Mourelatos Z., Dostie J., Paushkin S., et al. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 2002;16:720-728.[Abstract/Free Full Text]
• Narayanan U., Achsel T., Luhrmann R., Matera AG Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein. Mol Cell. 2004;16:223-234.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pellizzoni L., Baccon J., Charroux B., Dreyfuss G. The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1. Curr Biol. 2001;11:1079-1088.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Pellizzoni L., Charroux B., Dreyfuss G. SMN mutants of spinal muscular atrophy patients are defective in binding to snRNP proteins. Proc Natl Acad Sci USA. 1999;96:11167-11172.[Abstract/Free Full Text]
• Pellizzoni L., Charroux B., Rappsilber J., Mann M., Dreyfuss G. A functional interaction between the survival motor neuron complex and RNA polymerase II. J Cell Biol. 2001;152:75-85.[Abstract/Free Full Text]
• Pellizzoni L., Kataoka N., Charroux B., Dreyfuss G. A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell. 1998;95:615-624.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Will CL, Luhrmann R. Spliceosomal UsnRNP biogenesis, structure and function. Curr Opin Cell Biol. 2001;13:290-301.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kambach C., Walke S., Nagai K. Structure and assembly of the spliceosomal small nuclear ribonucleoprotein particles. Curr Opin Struct Biol. 1999;9:222-230.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Luhrmann R., Kastner B., Bach M. Structure of spliceosomal snRNPs and their role in pre-mRNA splicing. Biochim Biophys Acta. 1990;1087:265-292.[Medline] [Order article via Infotrieve]
• Meister G., Buhler D., Pillai R., Lottspeich F., Fischer U. A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs. Nat Cell Biol. 2001;3:945-949.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Achsel T., Stark H., Luhrmann R. The Sm domain is an ancient RNA-binding motif with oligo(U) specificity. Proc Natl Acad Sci USA. 2001;98:3685-3689.[Abstract/Free Full Text]
• Kambach C., Walke S., Young R., et al. Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell. 1999;96:375-387.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Stark H., Dube P., Luhrmann R., Kastner B. Arrangement of RNA and proteins in the spliceosomal U1 small nuclear ribonucleoprotein particle. Nature. 2001;409:539-542.[CrossRef][Medline] [Order article via Infotrieve]
• Mattaj IW Cap trimethylation of U snRNA is cytoplasmic and dependent on U snRNP protein binding. Cell. 1986;46:905-911.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Fischer U., Luhrmann R. An essential signaling role for the m3G cap in the transport of U1 snRNP to the nucleus. Science. 1990;249:786-790.[Abstract/Free Full Text]
• Fischer U., Sumpter V., Sekine M., Satoh T., Luhrmann R. Nucleo-cytoplasmic transport of U snRNPs: definition of a nuclear location signal in the Sm core domain that binds a transport receptor independently of the m3G cap. EMBO J. 1993;12:573-583.[Web of Science][Medline] [Order article via Infotrieve]
• Hamm J., Darzynkiewicz E., Tahara SM, Mattaj IW The trimethylguanosine cap structure of U1 snRNA is a component of a bipartite nuclear targeting signal. Cell. 1990;62:569-577.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Mattaj IW, Boelens W., Izaurralde E., Jarmolowski A., Kambach C. Nucleocytoplasmic transport and snRNP assembly. Mol Biol Rep. 1993;18:79-83.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Golembe TJ, Yong J., Dreyfuss G. Specific sequence features, recognized by the SMN complex, identify snRNAs and determine their fate as snRNPs. Mol Cell Biol. 2005;25:10989-11004.[Abstract/Free Full Text]
• Lee SI, Steitz JA Herpesvirus saimiri U RNAs are expressed and assembled into ribonucleoprotein particles in the absence of other viral genes. J Virol. 1990;64:3905-3915.[Abstract/Free Full Text]
• Battle DJ, Lau CK, Wan L., Deng H., Lotti F., Dreyfuss G. The Gemin5 protein of the SMN complex identifies snRNAs. Mol Cell. 2006;23:273-279.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Wan L., Battle DJ, Yong J., et al. The survival of motor neurons protein determines the capacity for snRNP assembly: biochemical deficiency in spinal muscular atrophy. Mol Cell Biol. 2005;25:5543-5551.[Abstract/Free Full Text]
• Feng W., Gubitz AK, Wan L., et al. Gemins modulate the expression and activity of the SMN complex. Hum Mol Genet. 2005;14:1605-1611.[Abstract/Free Full Text]
• Gabanella F., Carissimi C., Usiello A., Pellizzoni L. The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation. Hum Mol Genet. 2005;14: 3629-3642.[Abstract/Free Full Text]
• Winkler C., Eggert C., Gradl D., et al. Reduced U snRNP assembly causes motor axon degeneration in an animal model for spinal muscular atrophy. Genes Dev. 2005;19:2320-2330.[Abstract/Free Full Text]
• Giavazzi A., Setola V., Simonati A., Battaglia G. Neuronal-specific roles of the survival motor neuron protein: evidence from survival motor neuron expression patterns in the developing human central nervous system. J Neuropathol Exp Neurol. 2006;65:267-277.[Web of Science][Medline] [Order article via Infotrieve]
• Carrel TL, McWhorter ML, Workman E., et al. Survival motor neuron function in motor axons is independent of functions required for small nuclear ribonucleoprotein biogenesis. J Neurosci. 2006;26:11014-11022.[Abstract/Free Full Text]
• Zhang H., Xing L., Rossoll W., Wichterle H., Singer RH, Bassell GJ Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons. J Neurosci. 2006;26:8622-8632.[Abstract/Free Full Text]
• Rossoll W., Jablonka S., Andreassi C., et al. Smn, the spinal muscular atrophy-determining gene product, modulates axon growth and localization of beta-actin mRNA in growth cones of motoneurons. J Cell Biol. 2003;163:801-812.[Abstract/Free Full Text]

Journal of Child Neurology, Vol. 22, No. 8, 990-994 (2007)
DOI: 10.1177/0883073807305666


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				R. A. Brumback Child Neurologists Should Be Interested In Brain Tumors! J Child Neurol, November 1, 2009; 24(11): 1338 - 1340. [PDF]

				C. G. Bonnemann and R. S. Finkel Linking SMN to SMA: An assay for the rescuer Neurology, November 25, 2008; 71(22): 1752 - 1753. [Full Text] [PDF]

				M. P. Walker, T.K. Rajendra, L. Saieva, J. L. Fuentes, L. Pellizzoni, and A. G. Matera SMN complex localizes to the sarcomeric Z-disc and is a proteolytic target of calpain Hum. Mol. Genet., November 1, 2008; 17(21): 3399 - 3410. [Abstract] [Full Text] [PDF]

				S. B. Patel and M. Bellini The assembly of a spliceosomal small nuclear ribonucleoprotein particle Nucleic Acids Res., November 1, 2008; 36(20): 6482 - 6493. [Abstract] [Full Text] [PDF]

				L. Trinkle-Mulcahy, S. Boulon, Y. W. Lam, R. Urcia, F.-M. Boisvert, F. Vandermoere, N. A. Morrice, S. Swift, U. Rothbauer, H. Leonhardt, et al. Identifying specific protein interaction partners using quantitative mass spectrometry and bead proteomes J. Cell Biol., October 20, 2008; 183(2): 223 - 239. [Abstract] [Full Text] [PDF]

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Kolb, S. J. Articles by Dreyfuss, G. Search for Related Content PubMed PubMed Citation Articles by Kolb, S. J. Articles by Dreyfuss, G. Social Bookmarking                         What's this?