Li Darrick K, Tisdale Sarah, Lotti Francesco, Pellizzoni Livio
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.
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.
Semin Cell Dev Biol. 2014 Aug;32:22-9. doi: 10.1016/j.semcdb.2014.04.026. Epub 2014 Apr 24.
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.
在转录后水平，蛋白质编码基因的表达受一系列RNA调控事件的控制，包括初级转录本的核加工、成熟mRNA转运至特定细胞区室、翻译以及最终的周转。这些过程通过mRNA与RNA结合蛋白和核糖核蛋白（RNP）复合物的动态结合来协调。RNP在体内的精确形成对细胞发育和功能至关重要，其受损往往会导致人类疾病。生存运动神经元（SMN）蛋白是这一生物学范式的关键：SMN对于在mRNA加工中发挥作用的各种RNP的生物合成至关重要，导致SMN缺乏的基因突变会引起神经退行性疾病脊髓性肌萎缩症。在此，我们综述了SMN通过其在RNP组装中的多种功能在基因表达调控中不断扩展的作用。我们讨论了在理解SMN作为RNP伴侣的活性方面取得的进展，以及依赖SMN的RNA途径的破坏如何导致运动神经元疾病。
