title: The promoters of the survival motor neuron gene (SMN) and its copy (SMNc) share common regulatory elements.
abstract: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord. The survival motor neuron gene (SMN) has been recognized as the disease-causing gene. SMN is duplicated, and the almost identical copy gene (SMNc) remains functional in patients with SMA. The expression level of SMNc is tightly correlated with the clinical severity of the disease. Here, we define the transcription initiation site, delineate the region containing promoter activity, and analyze the sequence of the promoter region of both SMN and SMNc. We show that the promoter sequence and activity of the two genes are quasi identical, providing strong evidence for similar transcription regulation of the two genes. Therefore, the difference in the level of protein encoded by SMN and SMNc is the result of either different regulatory region(s) further apart or different posttranscriptional regulation. Interestingly, sequence analysis of the promoter region revealed several consensus binding sites for transcription factors. Therefore, the identification of transcription factors involved in the regulation of SMNc gene expression may lead to attractive strategies for therapy in SMA.
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, CNRS, Université Louis Pasteur, Strasbourg, France.
authors: A
authors: A
authors: Echaniz-Laguna
authors: P
authors: P
authors: Miniou
authors: D
authors: D
authors: Bartholdi
authors: J
authors: J
authors: Melki
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016601:RNA-Binding Proteins; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D055532:SMN Complex Proteins; D055540:Survival of Motor Neuron 2 Protein; D015533:Transcriptional Activation
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein