Small nuclear RNAs and mRNAs: linking RNA processing and transport to spinal muscular atrophy.

The splicing of pre-mRNA by the spliceosome is a characteristic feature of eukaryotic cells, dependent on a group of snRNPs (small nuclear ribonucleoproteins). These splicing snRNPs have a complex assembly pathway involving multiple steps that take place in different regions of the cell, which is reflected in their complex subcellular distribution. Vital to the assembly of splicing snRNPs is the protein SMN (survival of motor neurons). In multicellular organisms, SMN acts in the cytoplasm, together with its associated protein complex to assemble a heptameric ring of proteins called the Sm proteins as an early stage in splicing snRNP assembly. A deficiency of the SMN protein results in the inherited neurodegenerative condition SMA (spinal muscular atrophy), a leading cause of infant mortality specifically affecting spinal motor neurons. It has long been a puzzle how lowered levels of a protein required for a process as fundamental as splicing snRNP assembly can result in a condition with such a definite cell-type-specificity. The present review highlights recent research that points to wider roles in RNA metabolism for both SMN itself and the Sm proteins with which it is linked.