Survival motor neuron (SMN) protein in rat is expressed as different molecular forms and is developmentally regulated.
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by a progressive degeneration of motoneurons in spinal cord and brainstem. The telomeric copy of a duplicated gene termed survival motor neuron (smn), which maps to chromosome 5q13, has been found to be deleted in most patients. The encoded gene product is a novel protein which recently has been shown to accumulate in specific nuclear organelles (gemini of coiled bodies, GEMS), and to play a part in the formation of the spliceosome complex. We have cloned and sequenced the rat smn cDNA. Antibodies generated against an N-terminus peptide recognized a main protein of 32 kDa in immunoblots of rat embryonic tissue extracts. Minor bands of 35 kDa, 45 kDa and, in perinatal muscle, of 24 kDa were also specifically detected, indicating that SMN is expressed as different molecular forms. Subcellular fractionation indicated that the 32 kDa form is mainly soluble, while the 35 kDa and 45 kDa products segregate to the microsomal-mitochondrial fraction. SMN protein is highly regulated during development: expression is high in embryonic tissues (central nervous system, muscle, lung and liver), and then progressively decreases to very low levels in most tissues of the adult. The demonstration of different molecular forms of SMN along with its developmental regulation may help to understand the contribution of this protein in the appearance of SMA phenotype.
La Bella
V
V
INSERM U.382, Developmental Biology Institute of Marseille (IBDM) (CNRS-INSERM-Université de la Méditerranée-AP Marseille), France.
Cisterni
C
C
Salaün
D
D
Pettmann
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D016601:RNA-Binding Proteins; D051381:Rats; D055532:SMN Complex Proteins; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000166:cytology; D055533:Survival of Motor Neuron 1 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein