Pellizzoni Livio, Yong Jeongsik, Dreyfuss Gideon
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6148, USA.
Science. 2002 Nov 29;298(5599):1775-9. doi: 10.1126/science.1074962.
The Survival of Motor Neurons (SMN) protein, the product of the spinal muscular atrophy-determining gene, is part of a large macromolecular complex (SMN complex) that functions in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). Using cell extracts and purified components, we demonstrated that the SMN complex is necessary and sufficient to mediate the ATP-dependent assembly of the core of seven Sm proteins on uridine-rich, small nuclear ribonucleic acids (U snRNAs). In vitro experiments revealed strict requirements for ordered binding of the Sm proteins and the U snRNAs to the SMN complex. Importantly, the SMN complex is necessary to ensure that Sm cores assemble only on correct RNA targets and prevent their otherwise promiscuous association with other RNAs. Thus, the SMN complex functions as a specificity factor essential for the efficient assembly of Sm proteins on U snRNAs and likely protects cells from illicit, and potentially deleterious, nonspecific binding of Sm proteins to RNAs.
运动神经元存活（SMN）蛋白是脊髓性肌萎缩症决定基因的产物，是一种大型大分子复合物（SMN复合物）的一部分，该复合物在剪接体小核核糖核蛋白（snRNP）的组装中发挥作用。利用细胞提取物和纯化成分，我们证明SMN复合物对于介导富含尿苷的小核核糖核酸（U snRNA）上七种Sm蛋白核心的ATP依赖性组装是必要且充分的。体外实验揭示了Sm蛋白和U snRNA与SMN复合物有序结合的严格要求。重要的是，SMN复合物对于确保Sm核心仅在正确的RNA靶标上组装并防止它们与其他RNA发生随意结合是必要的。因此，SMN复合物作为一种特异性因子，对于Sm蛋白在U snRNA上的有效组装至关重要，并且可能保护细胞免受Sm蛋白与RNA的非法且可能有害的非特异性结合。
