Gubitz Amelie K, Mourelatos Zissimos, Abel Linda, Rappsilber Juri, Mann Matthias, Dreyfuss Gideon
Howard Hughes Medical Institute, Department of Biochemistry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
J Biol Chem. 2002 Feb 15;277(7):5631-6. doi: 10.1074/jbc.M109448200. Epub 2001 Nov 19.
The survival of motor neurons (SMN) protein is the product of the disease gene of spinal muscular atrophy and is found both in the cytoplasm and the nucleus, where it is concentrated in gems. SMN is part of a multi-protein complex that includes Gemin2, Gemin3, and Gemin4. The SMN complex plays an important role in the cytoplasmic assembly of small nuclear ribonucleoproteins (snRNPs) and likely other RNPs in pre-mRNA splicing and in the assembly of transcriptosomes. Here, we report the identification of an additional component of the SMN complex, a novel WD repeat protein termed Gemin5. Gemin5 binds SMN directly and is a component of the SMN complex. Furthermore, Gemin5 interacts with several of the snRNP core proteins including SmB, SmD1, SmD2, SmD3, and SmE, suggesting that it participates in the activities of the SMN complex in snRNP assembly. Immunolocalization studies demonstrate that Gemin5 is found in the cytoplasm and in the nucleus, where it colocalizes with SMN in gems. The presence of 13 WD repeat domains in the amino-terminal half of Gemin5 and a coiled-coil motif near its carboxyl terminus indicate that it may form a large heteromeric complex and engage in multiple interactions.
运动神经元存活蛋白（SMN）是脊髓性肌萎缩症疾病基因的产物，在细胞质和细胞核中均有发现，且在核宝石样结构中高度富集。SMN是一个多蛋白复合物的组成部分，该复合物包括Gemin2、Gemin3和Gemin4。SMN复合物在小核核糖核蛋白（snRNP）的细胞质组装以及在前体mRNA剪接中的其他核糖核蛋白组装和转录体组装过程中发挥重要作用。在此，我们报告了SMN复合物另一个组分的鉴定结果，即一种名为Gemin5的新型WD重复蛋白。Gemin5直接与SMN结合，是SMN复合物的一个组分。此外，Gemin5与几种snRNP核心蛋白相互作用，包括SmB、SmD1、SmD2、SmD3和SmE，这表明它参与了SMN复合物在snRNP组装中的活动。免疫定位研究表明，Gemin5存在于细胞质和细胞核中，且在核宝石样结构中与SMN共定位。Gemin5氨基末端的一半含有13个WD重复结构域，其羧基末端附近有一个卷曲螺旋基序，这表明它可能形成一个大型异源复合物并参与多种相互作用。
