Molecular mechanisms in spinal muscular atrophy: models and perspectives

M Sendtner - Current opinion in neurology, 2001 - journals.lww.com
Current opinion in neurology, 2001journals.lww.com
Spinal muscular atrophy is an autosomal-recessive disorder that is caused by homozygous
mutations or deletion of the telomeric copy of the survival of motor neurone (SMN) gene on
human chromosome 5q13. The SMN gene is present as an inverted repeat in this
chromosomal region, and both SMN genes are expressed. They differ by the preferential
expression of a full-length transcript from the telomeric copy and a truncated SMN protein
from the centromeric SMN gene, which lacks the carboxyl-terminal portions of the protein …
Abstract
Spinal muscular atrophy is an autosomal-recessive disorder that is caused by homozygous mutations or deletion of the telomeric copy of the survival of motor neurone (SMN) gene on human chromosome 5q13. The SMN gene is present as an inverted repeat in this chromosomal region, and both SMN genes are expressed. They differ by the preferential expression of a full-length transcript from the telomeric copy and a truncated SMN protein from the centromeric SMN gene, which lacks the carboxyl-terminal portions of the protein encoded by exon 7. The SMN protein is part of multiprotein complexes in the cytoplasm and the nucleus that are involved in spliceosomal small-nuclear RNP assembly. This function depends on interaction with spliceosomal Sm core proteins. Recent data have also shown that the SMN protein interacts with RNA polymerase II, thus implying additional functions in messenger RNA transcription, possibly by assembly of RNA polymerase II transcription complexes. Thus, the SMN protein is involved in critical steps of messenger RNA transcription and processing, and current research efforts are directed at identifying the specificity of these defects for the pathophysiological changes in motor neurones that occur in spinal muscular atrophy.
Lippincott Williams & Wilkins