SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease.
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.
Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Darrick K
DK
Li
Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Sarah
S
Tisdale
Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Francesco
F
Lotti
Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. Electronic address: lp2284@cumc.columbia.edu.
Livio
L
Pellizzoni
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D008957:Models, Genetic; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism*; D012326:RNA Splicing; D020871:RNA Stability; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D055532:SMN Complex Proteins / Q000235:genetics / Q000378:metabolism*
D012261:Ribonucleoproteins; D055532:SMN Complex Proteins
RNA processing; Ribonucleoprotein complexes (RNPs); Sm and LSm proteins; Small nuclear RNA (snRNA); Spinal muscular atrophy (SMA); Survival motor neuron (SMN)