SMN Mutants of Spinal Muscular Atrophy Patients Are Defective in Binding to snRNP Proteins
Spinal muscular atrophy (SMA) is a common motor neuron degenerative disease and the leading genetic cause of death of young children. The survival of motor neurons (SMN) gene, the SMA disease gene, is homozygously deleted or mutated in more than 98% of SMA patients. The SMN protein interacts with it...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 20; pp. 11167 - 11172 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences of the United States of America
28.09.1999
National Acad Sciences The National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Spinal muscular atrophy (SMA) is a common motor neuron degenerative disease and the leading genetic cause of death of young children. The survival of motor neurons (SMN) gene, the SMA disease gene, is homozygously deleted or mutated in more than 98% of SMA patients. The SMN protein interacts with itself, with SMN-interacting protein 1, and with several spliceosomal small nuclear ribonucleoprotein (snRNP) Sm proteins. A complex containing SMN plays a critical role in spliceosomal snRNP assembly and in pre-mRNA splicing. SMN mutants found in SMA patients show reduced self-association and lack the capacity to regenerate the splicing machinery. Here we demonstrate that SMN mutants found in SMA patients are defective in binding to Sm proteins. Moreover, we show that SMN, but not mutants found in SMA patients, can form large oligomers and that SMN oligomerization is required for high-affinity binding to spliceosomal snRNP Sm proteins. These findings directly link the impaired interaction between SMN and Sm proteins to a defect in snRNP metabolism and to SMA. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by Christine Guthrie, University of California, San Francisco, CA, and approved July 23, 1999 To whom reprint requests should be addressed. E-mail: gdreyfuss@hhmi.upenn.edu. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.96.20.11167 |