Spinal muscular atrophy: the RNP connection.
Degenerated motor neurons in the spinal cord are the pathological hallmark of spinal muscular atrophy (SMA). SMA is caused by mutations in the ubiquitously expressed survival motor neuron 1 (SMN1) gene, which lead to reduced levels of functional SMN protein. Many different functions have been assigned to SMN, including assembly of ribonucleoproteins (RNPs), splicing, transcription and axonal mRNA transport. Recently, tissue from SMA patients and animal models has been used to determine which function of SMN is affected in SMA patients. A surprising picture has emerged: the impaired assembly of RNP subunits of the spliceosome seems to be responsible for SMA pathogenesis. Here, we present a model of how this defect might cause motor-neuron degeneration and consider potential therapies.
Eggert
Christian
C
Theodor Boveri Institute, Biocenter at the University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
Chari
Ashwin
A
Laggerbauer
Bernhard
B
Fischer
Utz
U
D017398:Alternative Splicing; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein