The Spinal Muscular Atrophy Disease Gene Product, SMN: A Link between snRNP Biogenesis and the Cajal (Coiled) Body

doi:10.1083/jcb.147.4.715

This Article

	Full Text
	PDF (Full Text)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Carvalho, T.
	Articles by Carmo-Fonseca, M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Carvalho, T.
	Articles by Carmo-Fonseca, M.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/1999/11/715/ $5.00
The Journal of Cell Biology, Volume 147, Number 4, November 15, 1999 715-728

Original Article

The Spinal Muscular Atrophy Disease Gene Product, SMN: A Link between snRNP Biogenesis and the Cajal (Coiled) Body

Teresa Carvalho^a, Fátima Almeida^a, Alexandre Calapez^a, Miguel Lafarga^b, Maria T. Berciano^b, and Maria Carmo-Fonseca^a
^a Institute of Histology and Embryology, Faculty of Medicine, University of Lisbon, 1649-028 Lisboa Codex, Portugal
^b Department of Anatomy and Cell Biology, Faculty of Medicine, University of Cantabria, 39011 Santander, Spain

Correspondence to: Maria Carmo-Fonseca, Institute of Histology and Embryology, Faculty of Medicine, Av. Prof. Egas Moniz, 1649-028 Lisboa Codex, Portugal. Tel:+351 1 7934340 Fax:+351 1 7951780 E-mail:hcarmo{at}correio.fm.ul.pt.

The spliceosomal snRNAs U1, U2, U4, and U5 are synthesized inthe nucleus, exported to the cytoplasm to assemble with Sm proteins,and reimported to the nucleus as ribonucleoprotein particles.Recently, two novel proteins involved in biogenesis of smallnuclear ribonucleoproteins (snRNPs) were identified, the Spinalmuscular atrophy disease gene product (SMN) and its associatedprotein SIP1. It was previously reported that in HeLa cells,SMN and SIP1 form discrete foci located next to Cajal (coiled)bodies, the so-called "gemini of coiled bodies" or "gems." Anintriguing feature of gems is that they do not appear to containsnRNPs. Here we show that gems are present in a variable butsmall proportion of rapidly proliferating cells in culture.In the vast majority of cultured cells and in all primary neuronsanalyzed, SMN and SIP1 colocalize precisely with snRNPs in theCajal body. The presence of SMN and SIP1 in Cajal bodies isconfirmed by immunoelectron microscopy and by microinjectionof antibodies that interfere with the integrity of the structure.The association of SMN with snRNPs and coilin persists duringcell division, but at the end of mitosis there is a lag periodbetween assembly of new Cajal bodies in the nucleus and detectionof SMN in these structures, suggesting that SMN is targetedto preformed Cajal bodies. Finally, treatment of cells withleptomycin B (a drug that blocks export of U snRNAs to the cytoplasmand consequently import of new snRNPs into the nucleus) is shownto deplete snRNPs (but not SMN or SIP1) from the Cajal body.This suggests that snRNPs flow through the Cajal body duringtheir biogenesis pathway.

Key Words: Cajal (coiled) body, leptomycin B, nucleocytoplasmic transport,SMN protein, spliceosomal small nuclear ribonucleoproteins

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

This article has been cited by other articles:

Stanek, D., Pridalova-Hnilicova, J., Novotny, I., Huranova, M., Blazikova, M., Wen, X., Sapra, A. K., Neugebauer, K. M. (2008). Spliceosomal Small Nuclear Ribonucleoprotein Particles Repeatedly Cycle through Cajal Bodies. Mol. Biol. Cell 19: 2534-2543 [Abstract] [Full Text]
Tadesse, H., Deschenes-Furry, J., Boisvenue, S., Cote, J. (2008). KH-type splicing regulatory protein interacts with survival motor neuron protein and is misregulated in spinal muscular atrophy. Hum Mol Genet 17: 506-524 [Abstract] [Full Text]
Petri, S., Grimmler, M., Over, S., Fischer, U., Gruss, O. J. (2007). Dephosphorylation of survival motor neurons (SMN) by PPM1G/PP2C{gamma} governs Cajal body localization and stability of the SMN complex. J. Cell Biol. 179: 451-465 [Abstract] [Full Text]
Sleeman, J. (2007). A regulatory role for CRM1 in the multi-directional trafficking of splicing snRNPs in the mammalian nucleus. J. Cell Sci. 120: 1540-1550 [Abstract] [Full Text]
Zhang, H., Xing, L., Rossoll, W., Wichterle, H., Singer, R. H., Bassell, G. J. (2006). Multiprotein Complexes of the Survival of Motor Neuron Protein SMN with Gemins Traffic to Neuronal Processes and Growth Cones of Motor Neurons.. J. Neurosci. 26: 8622-8632 [Abstract] [Full Text]
Lemm, I., Girard, C., Kuhn, A. N., Watkins, N. J., Schneider, M., Bordonne, R., Luhrmann, R. (2006). Ongoing U snRNP Biogenesis Is Required for the Integrity of Cajal Bodies. Mol. Biol. Cell 17: 3221-3231 [Abstract] [Full Text]
Girard, C., Neel, H., Bertrand, E., Bordonne, R. (2006). Depletion of SMN by RNA interference in HeLa cells induces defects in Cajal body formation. Nucleic Acids Res 34: 2925-2932 [Abstract] [Full Text]
Li, L., Roy, K., Katyal, S., Sun, X., Bleoo, S., Godbout, R. (2006). Dynamic Nature of Cleavage Bodies and Their Spatial Relationship to DDX1 Bodies, Cajal Bodies, and Gems. Mol. Biol. Cell 17: 1126-1140 [Abstract] [Full Text]
Renvoise, B., Khoobarry, K., Gendron, M.-C., Cibert, C., Viollet, L., Lefebvre, S. (2006). Distinct domains of the spinal muscular atrophy protein SMN are required for targeting to Cajal bodies in mammalian cells. J. Cell Sci. 119: 680-692 [Abstract] [Full Text]
Shpargel, K. B., Matera, A. G. (2005). Gemin proteins are required for efficient assembly of Sm-class ribonucleoproteins. Proc. Natl. Acad. Sci. USA 102: 17372-17377 [Abstract] [Full Text]
Santama, N., Ogg, S. C., Malekkou, A., Zographos, S. E., Weis, K., Lamond, A. I. (2005). Characterization of hCINAP, a Novel Coilin-interacting Protein Encoded by a Transcript from the Transcription Factor TAFIID32 Locus. J. Biol. Chem. 280: 36429-36441 [Abstract] [Full Text]
Feng, W., Gubitz, A. K., Wan, L., Battle, D. J., Dostie, J., Golembe, T. J., Dreyfuss, G. (2005). Gemins modulate the expression and activity of the SMN complex. Hum Mol Genet 14: 1605-1611 [Abstract] [Full Text]
Dundr, M., Hebert, M. D., Karpova, T. S., Stanek, D., Xu, H., Shpargel, K. B., Meier, U. T., Neugebauer, K. M., Matera, A. G., Misteli, T. (2004). In vivo kinetics of Cajal body components. J. Cell Biol. 164: 831-842 [Abstract] [Full Text]
Muresan, Z., Muresan, V. (2004). A phosphorylated, carboxy-terminal fragment of {beta}-amyloid precursor protein localizes to the splicing factor compartment. Hum Mol Genet 13: 475-488 [Abstract] [Full Text]
Zhu, Y., Tomlinson, R. L., Lukowiak, A. A., Terns, R. M., Terns, M. P. (2004). Telomerase RNA Accumulates in Cajal Bodies in Human Cancer Cells. Mol. Biol. Cell 15: 81-90 [Abstract] [Full Text]
Rossoll, W., Jablonka, S., Andreassi, C., Kroning, A.-K., Karle, K., Monani, U. R., Sendtner, M. (2003). 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. 163: 801-812 [Abstract] [Full Text]
Zhang, H. L., Pan, F., Hong, D., Shenoy, S. M., Singer, R. H., Bassell, G. J. (2003). Active Transport of the Survival Motor Neuron Protein and the Role of Exon-7 in Cytoplasmic Localization. J. Neurosci. 23: 6627-6637 [Abstract] [Full Text]
Carnegie, G. K., Sleeman, J. E., Morrice, N., Hastie, C. J., Peggie, M. W., Philp, A., Lamond, A. I., Cohen, P. T. W. (2003). Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNPs. J. Cell Sci. 116: 1905-1913 [Abstract] [Full Text]
Sleeman, J. E., Trinkle-Mulcahy, L., Prescott, A. R., Ogg, S. C., Lamond, A. I. (2003). Cajal body proteins SMN and Coilin show differential dynamic behaviour in vivo. J. Cell Sci. 116: 2039-2050 [Abstract] [Full Text]
Polak, P. E., Simone, F., Kaberlein, J. J., Luo, R. T., Thirman, M. J. (2003). ELL and EAF1 are Cajal Body Components That Are Disrupted in MLL-ELL Leukemia. Mol. Biol. Cell 14: 1517-1528 [Abstract] [Full Text]
Stanek, D., Rader, S. D., Klingauf, M., Neugebauer, K. M. (2003). Targeting of U4/U6 small nuclear RNP assembly factor SART3/p110 to Cajal bodies. J. Cell Biol. 160: 505-516 [Abstract] [Full Text]
Whitehead, S. E., Jones, K. W., Zhang, X., Cheng, X., Terns, R. M., Terns, M. P. (2002). Determinants of the Interaction of the Spinal Muscular Atrophy Disease Protein SMN with the Dimethylarginine-modified Box H/ACA Small Nucleolar Ribonucleoprotein GAR1. J. Biol. Chem. 277: 48087-48093 [Abstract] [Full Text]
Ogg, S. C., Lamond, A. I. (2002). Cajal bodies and coilin--moving towards function. J. Cell Biol. 159: 17-21 [Abstract] [Full Text]
Baccon, J., Pellizzoni, L., Rappsilber, J., Mann, M., Dreyfuss, G. (2002). Identification and Characterization of Gemin7, a Novel Component of the Survival of Motor Neuron Complex. J. Biol. Chem. 277: 31957-31962 [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]
Leung, A. K.L., Lamond, A. I. (2002). In vivo analysis of NHPX reveals a novel nucleolar localization pathway involving a transient accumulation in splicing speckles. J. Cell Biol. 157: 615-629 [Abstract] [Full Text]
Lefebvre, S., Burlet, P., Viollet, L., Bertrandy, S., Huber, C., Belser, C., Munnich, A. (2002). A novel association of the SMN protein with two major non-ribosomal nucleolar proteins and its implication in spinal muscular atrophy. Hum Mol Genet 11: 1017-1027 [Abstract] [Full Text]
Young, P. J., Jensen, K. T., Burger, L. R., Pintel, D. J., Lorson, C. L. (2002). Minute Virus of Mice NS1 Interacts with the SMN Protein, and They Colocalize in Novel Nuclear Bodies Induced by Parvovirus Infection. J. Virol. 76: 3892-3904 [Abstract] [Full Text]
Sleeman, J. E., Ajuh, P., Lamond, A. I. (2002). snRNP protein expression enhances the formation of Cajal bodies containing p80-coilin and SMN. J. Cell Sci. 114: 4407-4419 [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]
Jones, K. W., Gorzynski, K., Hales, C. M., Fischer, U., Badbanchi, F., Terns, R. M., Terns, M. P. (2001). Direct Interaction of the Spinal Muscular Atrophy Disease Protein SMN with the Small Nucleolar RNA-associated Protein Fibrillarin. J. Biol. Chem. 276: 38645-38651 [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. J. Cell Biol. 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. J. Cell Biol. 154: 293-308 [Abstract] [Full Text]
Platani, M., Goldberg, I., Swedlow, J. R., Lamond, A. I. (2000). In Vivo Analysis of Cajal Body Movement, Separation, and Joining in Live Human Cells. J. Cell Biol. 151: 1561-1574 [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]
Bordonné, R. (2000). Functional Characterization of Nuclear Localization Signals in Yeast Sm Proteins. Mol. Cell. Biol. 20: 7943-7954 [Abstract] [Full Text]
Snaar, , Wiesmeijer, , Jochemsen, A., Tanke, H., Dirks, R. (2000). Mutational Analysis of Fibrillarin and Its Mobility in Living Human Cells. J. Cell Biol. 151: 653-662 [Abstract] [Full Text]
Smith, K. P., Lawrence, J. B. (2000). Interactions of U2 Gene Loci and Their Nuclear Transcripts with Cajal (Coiled) Bodies: Evidence for PreU2 within Cajal Bodies. Mol. Biol. Cell 11: 2987-2998 [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. J. Cell Biol. 148: 1177-1186 [Abstract] [Full Text]
Misteli, T (2000). Cell biology of transcription and pre-mRNA splicing: nuclear architecture meets nuclear function. J. Cell Sci. 113: 1841-1849 [Abstract]
Liu, J, Hebert, M., Ye, Y, Templeton, D., Kung, H, Matera, A. (2000). Cell cycle-dependent localization of the CDK2-cyclin E complex in Cajal (coiled) bodies. J. Cell Sci. 113: 1543-1552 [Abstract]
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]
Young, P. J., Day, P. M., Zhou, J., Androphy, E. J., Morris, G. E., Lorson, C. L. (2002). A Direct Interaction between the Survival Motor Neuron Protein and p53 and Its Relationship to Spinal Muscular Atrophy. J. Biol. Chem. 277: 2852-2859 [Abstract] [Full Text]
Gubitz, A. K., Mourelatos, Z., Abel, L., Rappsilber, J., Mann, M., Dreyfuss, G. (2002). Gemin5, a Novel WD Repeat Protein Component of the SMN Complex That Binds Sm Proteins. J. Biol. Chem. 277: 5631-5636 [Abstract] [Full Text]
Pellizzoni, L., Baccon, J., Rappsilber, J., Mann, M., Dreyfuss, G. (2002). Purification of Native Survival of Motor Neurons Complexes and Identification of Gemin6 as a Novel Component. J. Biol. Chem. 277: 7540-7545 [Abstract] [Full Text]