
pmid: 16951947
Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. SMA is caused by the homozygous absence of survival motor neuron-1 (SMN1). SMN2, a nearly identical copy gene, is retained in all SMA patients and encodes an identical protein as SMN1; however, SMN1 and SMN2 differ by a silent C to T transition which results in the production of an alternatively spliced isoform (SMNDelta7), which encodes a defective protein, demonstrating that the absence of the short peptide encoded by SMN exon 7 is critical in SMA development. Previously, we have shown that for some functions heterologous sequences can compensate for the exon 7 peptide, suggesting that the SMN C-terminus functions non-specifically. Consistent with this hypothesis, we now identify novel aminoglycosides that can induce SMN protein levels in patient fibroblasts. This hypothesis was supported, in part, by a novel fluorescent SMN read-through assay. Interestingly, however, through the development of a SMN exon 7-specific antibody, results suggested that levels of normal full-length SMN might also be elevated by aminoglycoside treatment. These results demonstrate that the compounds that promote read-through may provide an alternative platform for the discovery of compounds that induce SMN protein levels.
Dose-Response Relationship, Drug, Molecular Structure, RNA Splicing, Recombinant Fusion Proteins, Blotting, Western, Green Fluorescent Proteins, Gene Expression, RNA-Binding Proteins, Nerve Tissue Proteins, Exons, Fibroblasts, Muscular Atrophy, Spinal, Aminoglycosides, Humans, Enzyme Inhibitors, Cyclic AMP Response Element-Binding Protein, Luciferases, Cells, Cultured, HeLa Cells, Histone Acetyltransferases
Dose-Response Relationship, Drug, Molecular Structure, RNA Splicing, Recombinant Fusion Proteins, Blotting, Western, Green Fluorescent Proteins, Gene Expression, RNA-Binding Proteins, Nerve Tissue Proteins, Exons, Fibroblasts, Muscular Atrophy, Spinal, Aminoglycosides, Humans, Enzyme Inhibitors, Cyclic AMP Response Element-Binding Protein, Luciferases, Cells, Cultured, HeLa Cells, Histone Acetyltransferases
| selected citations These citations are derived from selected sources. This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 93 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |
