Molecular and cellular basis of spinal muscular atrophy.

Autosomal recessive spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle atrophy combined with motor neuron degeneration. SMA is caused by homozygous mutation or loss of the telomeric copy of the survival of motor neuron gene (SMN). The SMN gene is localized as an inverted repeat on chromosome 5q13. Both gene copies (SMN1 and SMN2) are expressed, but they differ in the expression of full-length protein. SMN2 gene preferentially gives rise to a truncated and less stable version of the SMN protein and thus can not compensate for SMN1 loss or mutations unless it is not present in multiple copies. The SMN protein is part of multiprotein complexes in the cytoplasm and the nucleus of all cell types. These complexes are involved in assembly of spliceosomal snRNPs. SMN interacts with RNA polymerase II and other binding proteins, indicating that the SMN protein is involved in messenger and ribosomal RNA transcription and processing. The analysis of animal models for SMA could help to identify the pathophysiological changes that are responsible for spinal muscular atrophy.