A. Echaniz-laguna et al., The promoters of the survival motor neuron gene (SMN) and its copy (SMNc) share common regulatory elements, AM J HU GEN, 64(5), 1999, pp. 1365-1370
Citations number
24
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Molecular Biology & Genetics
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-c
ausing gene. SMN is duplicated, and the almost identical copy gene (SMNc) r
emains functional in patients with SMA. The expression level of SMNc is tig
htly 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 regula
tion of the two genes. Therefore, the difference in the level of protein en
coded 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 bindin
g sites for transcription factors. Therefore, the identification of transcr
iption factors involved in the regulation of SMNc gene expression may lead
to attractive strategies for therapy in SMA.