Abstract
The survival of motor neurons protein (SMN), the product of the neurodegenerative disease spinal muscular atrophy (SMA) gene, functions as an assembly factor for snRNPs and likely other RNPs. SMN binds the arginine- and glycine-rich (RG) domains of the snRNP proteins SmD1 and SmD3. Specific arginines in these domains are modified to dimethylarginines, a common modification of unknown function. We show that SMN binds preferentially to the dimethylarginine-modified RG domains of SmD1 and SmD3. The binding of other SMN-interacting proteins is also strongly enhanced by methylation. Thus, methylation of arginines is a novel mechanism to promote specific protein-protein interactions and appears to be key to generating high-affinity SMN substrates. It is reasonable to expect that protein hypomethylation may contribute to the severity of SMA.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Arginine / analogs & derivatives
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Arginine / metabolism*
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Autoantigens
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Cyclic AMP Response Element-Binding Protein
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Enzyme Inhibitors / pharmacology
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HeLa Cells
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Humans
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Methylation
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Molecular Sequence Data
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Muscular Atrophy, Spinal / etiology
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Muscular Atrophy, Spinal / genetics
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Nerve Tissue Proteins / metabolism*
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Protein Binding
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RNA-Binding Proteins
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Recombinant Fusion Proteins / metabolism
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Ribonucleoproteins, Small Nuclear / metabolism*
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SMN Complex Proteins
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Substrate Specificity
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snRNP Core Proteins
Substances
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Autoantigens
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Cyclic AMP Response Element-Binding Protein
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Enzyme Inhibitors
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Nerve Tissue Proteins
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RNA-Binding Proteins
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Recombinant Fusion Proteins
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Ribonucleoproteins, Small Nuclear
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SMN Complex Proteins
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SNRPD1 protein, human
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SNRPD3 protein, human
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SNRPN protein, human
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snRNP Core Proteins
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N,N-dimethylarginine
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Arginine