Price Phillip L, Morderer Dmytro, Rossoll Wilfried
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Department of Cell Biology, Emory University, Atlanta, GA, USA.
Adv Neurobiol. 2018;20:143-171. doi: 10.1007/978-3-319-89689-2_6.
Spinal muscular atrophy (SMA) is a motor neuron disease caused by mutations/deletions within the survival of motor neuron 1 (SMN1) gene that lead to a pathological reduction of SMN protein levels. SMN is part of a multiprotein complex, functioning as a molecular chaperone that facilitates the assembly of spliceosomal small nuclear ribonucleoproteins (snRNP). In addition to its role in spliceosome formation, SMN has also been found to interact with mRNA-binding proteins (mRBPs), and facilitate their assembly into mRNP transport granules. The association of protein and RNA in RNP complexes plays an important role in an extensive and diverse set of cellular processes that regulate neuronal growth, differentiation, and the maturation and plasticity of synapses. This review discusses the role of SMN in RNP assembly and localization, focusing on molecular defects that affect mRNA processing and may contribute to SMA pathology.
脊髓性肌萎缩症（SMA）是一种由运动神经元存活基因1（SMN1）内的突变/缺失引起的运动神经元疾病，这些突变/缺失导致SMN蛋白水平病理性降低。SMN是一种多蛋白复合物的一部分，作为分子伴侣发挥作用，促进剪接体小核核糖核蛋白（snRNP）的组装。除了在剪接体形成中的作用外，还发现SMN与mRNA结合蛋白（mRBP）相互作用，并促进它们组装成mRNP运输颗粒。RNP复合物中蛋白质与RNA的结合在一系列广泛多样的细胞过程中发挥重要作用，这些过程调节神经元的生长、分化以及突触的成熟和可塑性。本综述讨论了SMN在RNP组装和定位中的作用，重点关注影响mRNA加工并可能导致SMA病理的分子缺陷。
