Human Molecular Genetics, Vol 8, 2351-2357, Copyright © 1999 by Oxford University Press
D B#hler, V Raker, R L#hrmann and U Fischer
Spinal muscular atrophy (SMA) is a neurodegenerative disease of spinal
motor neurons caused by reduced levels of functional survival of motor
neurons (SMN) protein. SMN is part of a macromolecular complex that
contains the SMN-interacting protein 1 (SIP1) and spliceosomal Sm proteins.
Although it is clear that SIP1 as a component of this complex is essential
for spliceosomal uridine-rich small ribonucleoprotein (U snRNP) assembly,
the role of SMN and its functional interactions with SIP1 and Sm proteins
are poorly understood. Here we show that the central region of SMN
comprising a tudor domain facilitates direct binding to Sm proteins.
Strikingly, the SMA-causing missense mutation E134K within the tudor domain
severely reduced the ability of SMN to interact with Sm proteins. Moreover,
antibodies directed against the tudor domain prevent Sm protein binding to
SMN and abolish assembly of U snRNPs in vivo. Thus, our data show that SMN
is an essential U snRNP assembly factor and establish a direct correlation
between defects in the biogenesis of U snRNPs and SMA.
ARTICLES
Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: implications for spinal muscular atrophy
Max-Planck-Institut f#r Biochemie, Am Klopferspitz 18a, D-82152 Martinsried, Germany,
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S. Jablonka, M. Bandilla, S. Wiese, D. Buhler, B. Wirth, M. Sendtner, and U. Fischer Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy Hum. Mol. Genet., March 1, 2001; 10(5): 497 - 505. [Abstract] [Full Text] [PDF]
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B. Laggerbauer, D. Ostareck, E.-M. Keidel, A. Ostareck-Lederer, and U. Fischer Evidence that fragile X mental retardation protein is a negative regulator of translation Hum. Mol. Genet., February 1, 2001; 10(4): 329 - 338. [Abstract] [Full Text] [PDF]
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L. Pellizzoni, B. Charroux, J. Rappsilber, M. Mann, and G. Dreyfuss A Functional Interaction between the Survival Motor Neuron Complex and RNA Polymerase II J. Cell Biol., January 8, 2001; 152(1): 75 - 86. [Abstract] [Full Text] [PDF]
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P. J. Young, N. t. Man, C. L. Lorson, T. T. Le, E. J. Androphy, A. H.M. Burghes, and G. E. Morris The exon 2b region of the spinal muscular atrophy protein, SMN, is involved in self-association and SIP1 binding Hum. Mol. Genet., November 1, 2000; 9(19): 2869 - 2877. [Abstract] [Full Text] [PDF]
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G. Meister, D. Buhler, B. Laggerbauer, M. Zobawa, F. Lottspeich, and U. Fischer 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., August 12, 2000; 9(13): 1977 - 1986. [Abstract] [Full Text] [PDF]
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L. Campbell, K. M. D. Hunter, P. Mohaghegh, J. M. Tinsley, M. A. Brasch, and K. E. Davies Direct interaction of Smn with dp103, a putative RNA helicase: a role for Smn in transcription regulation? Hum. Mol. Genet., April 12, 2000; 9(7): 1093 - 1100. [Abstract] [Full Text] [PDF]
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S. Hannus, D. Buhler, M. Romano, B. Seraphin, and U. Fischer The Schizosaccharomyces pombe protein Yab8p and a novel factor, Yip1p, share structural and functional similarity with the spinal muscular atrophy-associated proteins SMN and SIP1 Hum. Mol. Genet., March 22, 2000; 9(5): 663 - 674. [Abstract] [Full Text] [PDF]
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N. Owen, C. L. Doe, J. Mellor, and K. E. Davies Characterization of the Schizosaccharomyces pombe orthologue of the human survival motor neuron (SMN) protein Hum. Mol. Genet., March 22, 2000; 9(5): 675 - 684. [Abstract] [Full Text] [PDF]
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S. Paushkin, B. Charroux, L. Abel, R. A. Perkinson, L. Pellizzoni, and G. Dreyfuss The Survival Motor Neuron Protein of Schizosacharomyces pombe. CONSERVATION OF SURVIVAL MOTOR NEURON INTERACTION DOMAINS IN DIVERGENT ORGANISMS J. Biol. Chem., July 28, 2000; 275(31): 23841 - 23846. [Abstract] [Full Text] [PDF]
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W. J. Friesen and G. Dreyfuss 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., August 18, 2000; 275(34): 26370 - 26375. [Abstract] [Full Text] [PDF]
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J. Wang and G. Dreyfuss 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., March 23, 2001; 276(13): 9599 - 9605. [Abstract] [Full Text] [PDF]
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L. R. Saunders, D. J. Perkins, S. Balachandran, R. Michaels, R. Ford, A. Mayeda, and G. N. Barber Characterization of Two Evolutionarily Conserved, Alternatively Spliced Nuclear Phosphoproteins, NFAR-1 and -2, That Function in mRNA Processing and Interact with the Double-stranded RNA-dependent Protein Kinase, PKR J. Biol. Chem., August 17, 2001; 276(34): 32300 - 32312. [Abstract] [Full Text] [PDF]
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J. Wang and G. Dreyfuss Characterization of Functional Domains of the SMN Protein in Vivo J. Biol. Chem., November 21, 2001; 276(48): 45387 - 45393. [Abstract] [Full Text] [PDF]
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A. K. Gubitz, Z. Mourelatos, L. Abel, J. Rappsilber, M. Mann, and G. Dreyfuss Gemin5, a Novel WD Repeat Protein Component of the SMN Complex That Binds Sm Proteins J. Biol. Chem., February 8, 2002; 277(7): 5631 - 5636. [Abstract] [Full Text] [PDF]
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L. Pellizzoni, J. Baccon, J. Rappsilber, M. Mann, and G. Dreyfuss Purification of Native Survival of Motor Neurons Complexes and Identification of Gemin6 as a Novel Component J. Biol. Chem., February 22, 2002; 277(9): 7540 - 7545. [Abstract] [Full Text] [PDF]
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