Putting some spine into alternative splicing.
Spinal muscular atrophy is a neurodegenerative disease caused by mutations of the SMN1 gene. The homologous SMN2 gene is unable to complement SMN1 because of a crucial mutation in an exonic splicing enhancer, leading to alternative splicing and exclusion of exon 7. Two recent papers show that the defect in splicing of exon 7 of SMN2 is specifically corrected by small synthetic effectors. These new and specific approaches have potential in the treatment of diseases caused by defective splicing.
Khoo
Bernard
B
Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK.
Akker
Scott A
SA
Chew
Shern L
SL
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D005091:Exons; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D015533:Transcriptional Activation
D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein