SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease

Abstract

At the post-transcriptional level, expression of protein-coding genes is controlled by a series of RNA regulatory events including nuclear processing of primary transcripts, transport of mature mRNAs to specific cellular compartments, translation and ultimately, turnover. These processes are orchestrated through the dynamic association of mRNAs with RNA binding proteins and ribonucleoprotein (RNP) complexes. Accurate formation of RNPs in vivo is fundamentally important to cellular development and function, and its impairment often leads to human disease. The survival motor neuron (SMN) protein is key to this biological paradigm: SMN is essential for the biogenesis of various RNPs that function in mRNA processing, and genetic mutations leading to SMN deficiency cause the neurodegenerative disease spinal muscular atrophy. Here we review the expanding role of SMN in the regulation of gene expression through its multiple functions in RNP assembly. We discuss advances in our understanding of SMN activity as a chaperone of RNPs and how disruption of SMN-dependent RNA pathways can cause motor neuron disease.

Keywords: RNA processing; Ribonucleoprotein complexes (RNPs); Sm and LSm proteins; Small nuclear RNA (snRNA); Spinal muscular atrophy (SMA); Survival motor neuron (SMN).

Figure 1. SMN-dependent RNP assembly pathways and their link to SMA

The SMN complex—depicted with known integral subunits according to [3]—and the protein and RNA components of each of its proposed RNP targets are shown above the RNA pathway in which they function. Solid arrows indicate connections that are established both molecularly and functionally.