Original Article

Gemin3: A Novel DEAD Box Protein that Interacts with SMN, the Spinal Muscular Atrophy Gene Product, and Is a Component of Gems

Correspondence to: Gideon Dreyfuss, Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148. Tel:(215) 898-0398 Fax:(215) 573-2000 E-mail:gdreyfuss{at}hhmi.upenn.edu.

The survival of motor neurons (SMN) gene is the disease gene of spinal muscular atrophy (SMA), a common motor neuron degenerative disease. The SMN protein is part of a complex containing several proteins, of which one, SIP1 (SMN interacting protein 1), has been characterized so far. The SMN complex is found in both the cytoplasm and in the nucleus, where it is concentrated in bodies called gems. In the cytoplasm, SMN and SIP1 interact with the Sm core proteins of spliceosomal small nuclear ribonucleoproteins (snRNPs), and they play a critical role in snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing, likely by serving in the regeneration of snRNPs. Here, we report the identification of another component of the SMN complex, a novel DEAD box putative RNA helicase, named Gemin3. Gemin3 interacts directly with SMN, as well as with SmB, SmD2, and SmD3. Immunolocalization studies using mAbs to Gemin3 show that it colocalizes with SMN in gems. Gemin3 binds SMN via its unique COOH-terminal domain, and SMN mutations found in some SMA patients strongly reduce this interaction. The presence of a DEAD box motif in Gemin3 suggests that it may provide the catalytic activity that plays a critical role in the function of the SMN complex on RNPs.

Key Words: helicase, nuclear bodies, DnRNP biogenesis, splicing, spinal muscular atrophy

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• Linder, P. (2006). Dead-box proteins: a family affair--active and passive players in RNP-remodeling. Nucleic Acids Res 34: 4168-4180 [Abstract] [Full Text]  
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• Anderson, K., Potter, A., Baban, D., Davies, K. E. (2003). Protein expression changes in spinal muscular atrophy revealed with a novel antibody array technology. Brain 126: 2052-2064 [Abstract] [Full Text]  
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• Yan, X., Mouillet, J.-F., Ou, Q., Sadovsky, Y. (2003). A Novel Domain within the DEAD-Box Protein DP103 Is Essential for Transcriptional Repression and Helicase Activity. Mol. Cell. Biol. 23: 414-423 [Abstract] [Full Text]  
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• Narayanan, U., Ospina, J. K., Frey, M. R., Hebert, M. D., Matera, A. G. (2002). SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin {beta}. Hum Mol Genet 11: 1785-1795 [Abstract] [Full Text]  
• Fan, L., Simard, L. R. (2002). Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development. Hum Mol Genet 11: 1605-1614 [Abstract] [Full Text]  
• Schwarz, D. S., Zamore, P. D. (2002). Why do miRNAs live in the miRNP?. Genes Dev. 16: 1025-1031 [Full Text]  
• Mourelatos, Z., Dostie, J., Paushkin, S., Sharma, A., Charroux, B., Abel, L., Rappsilber, J., Mann, M., Dreyfuss, G. (2002). miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 16: 720-728 [Abstract] [Full Text]  
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• Rossoll, W., Kroning, A.-K., Ohndorf, U.-M., Steegborn, C., Jablonka, S., Sendtner, M. (2002). Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons?. Hum Mol Genet 11: 93-105 [Abstract] [Full Text]  
• Friesen, W. J., Paushkin, S., Wyce, A., Massenet, S., Pesiridis, G. S., Van Duyne, G., Rappsilber, J., Mann, M., Dreyfuss, G. (2001). The Methylosome, a 20S Complex Containing JBP1 and pICln, Produces Dimethylarginine-Modified Sm Proteins. Mol. Cell. Biol. 21: 8289-8300 [Abstract] [Full Text]  
• Voss, M. D., Hille, A., Barth, S., Spurk, A., Hennrich, F., Holzer, D., Mueller-Lantzsch, N., Kremmer, E., Grasser, F. A. (2001). Functional Cooperation of Epstein-Barr Virus Nuclear Antigen 2 and the Survival Motor Neuron Protein in Transactivation of the Viral LMP1 Promoter. J. Virol. 75: 11781-11790 [Abstract] [Full Text]  
• Hebert, M. D., Szymczyk, P. W., Shpargel, K. B., Matera, A. G. (2001). Coilin forms the bridge between Cajal bodies and SMN, the Spinal Muscular Atrophy protein. Genes Dev. 15: 2720-2729 [Abstract] [Full Text]  
• Bleoo, S., Sun, X., Hendzel, M. J., Rowe, J. M., Packer, M., Godbout, R. (2001). Association of Human DEAD Box Protein DDX1 with a Cleavage Stimulation Factor Involved in 3'-End Processing of Pre-mRNA. Mol. Biol. Cell 12: 3046-3059 [Abstract] [Full Text]  
• Frey, M. R., Matera, A. G. (2001). RNA-mediated interaction of Cajal bodies and U2 snRNA genes. JCB 154: 499-510 [Abstract] [Full Text]  
• Tucker, K. E., Berciano, M. T., Jacobs, E. Y., LePage, D. F., Shpargel, K. B., Rossire, J. J., Chan, E. K.L., Lafarga, M., Conlon, R. A., Matera, A. G. (2001). Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product. JCB 154: 293-308 [Abstract] [Full Text]  
• Jablonka, S., Bandilla, M., Wiese, S., Buhler, D., Wirth, B., Sendtner, M., Fischer, U. (2001). Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy. Hum Mol Genet 10: 497-505 [Abstract] [Full Text]  
• Pellizzoni, L., Charroux, B., Rappsilber, J., Mann, M., Dreyfuss, G. (2001). A Functional Interaction between the Survival Motor Neuron Complex and RNA Polymerase II. JCB 152: 75-86 [Abstract] [Full Text]  
• Ou, Q., Mouillet, J.-F., Yan, X., Dorn, C., Crawford, P. A., Sadovsky, Y. (2001). The DEAD Box Protein DP103 Is a Regulator of Steroidogenic Factor-1. Mol. Endocrinol. 15: 69-79 [Abstract] [Full Text]  
• Hebert, M. D., Matera, A. G. (2000). Self-association of Coilin Reveals a Common Theme in Nuclear Body Localization. Mol. Biol. Cell 11: 4159-4171 [Abstract] [Full Text]  
• Kerr, D. A., Nery, J. P., Traystman, R. J., Chau, B. N., Hardwick, J. M. (2000). Survival motor neuron protein modulates neuron-specific apoptosis. Proc. Natl. Acad. Sci. USA 10.1073/pnas.230364197v1 [Abstract] [Full Text]  
• Monani, U. R., Coovert, D. D., Burghes, A. H.M. (2000). Animal models of spinal muscular atrophy. Hum Mol Genet 9: 2451-2457 [Abstract] [Full Text]  
• Meister, G., Buhler, D., Laggerbauer, B., Zobawa, M., Lottspeich, F., Fischer, U. (2000). 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 9: 1977-1986 [Abstract] [Full Text]  
• Campbell, L., Hunter, K. M. D., Mohaghegh, P., Tinsley, J. M., Brasch, M. A., Davies, K. E. (2000). Direct interaction of Smn with dp103, a putative RNA helicase: a role for Smn in transcription regulation?. Hum Mol Genet 9: 1093-1100 [Abstract] [Full Text]  
• Charroux, B., Pellizzoni, L., Perkinson, R. A., Yong, J., Shevchenko, A., Mann, M., Dreyfuss, G. (2000). Gemin4: A Novel Component of the SMN Complex That Is Found in both Gems and Nucleoli. JCB 148: 1177-1186 [Abstract] [Full Text]  
• Paushkin, S., Charroux, B., Abel, L., Perkinson, R. A., Pellizzoni, L., Dreyfuss, G. (2000). The Survival Motor Neuron Protein of Schizosacharomyces pombe. CONSERVATION OF SURVIVAL MOTOR NEURON INTERACTION DOMAINS IN DIVERGENT ORGANISMS. J. Biol. Chem. 275: 23841-23846 [Abstract] [Full Text]  
• Friesen, W. J., Dreyfuss, G. (2000). 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. 275: 26370-26375 [Abstract] [Full Text]  
• Wang, J., Dreyfuss, G. (2001). A Cell System with Targeted Disruption of the SMN Gene. FUNCTIONAL CONSERVATION OF THE SMN PROTEIN AND DEPENDENCE OF Gemin2 ON SMN. J. Biol. Chem. 276: 9599-9605 [Abstract] [Full Text]  
• Rappsilber, J., Ajuh, P., Lamond, A. I., Mann, M. (2001). SPF30 Is an Essential Human Splicing Factor Required for Assembly of the U4/U5/U6 Tri-small Nuclear Ribonucleoprotein into the Spliceosome. J. Biol. Chem. 276: 31142-31150 [Abstract] [Full Text]  
• Wang, J., Dreyfuss, G. (2001). Characterization of Functional Domains of the SMN Protein in Vivo. J. Biol. Chem. 276: 45387-45393 [Abstract] [Full Text]  
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• Kerr, D. A., Nery, J. P., Traystman, R. J., Chau, B. N., Hardwick, J. M. (2000). Survival motor neuron protein modulates neuron-specific apoptosis. Proc. Natl. Acad. Sci. USA 97: 13312-13317 [Abstract] [Full Text]  

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