The Schizosaccharomyces pombe protein Yab8p and a novel factor, Yip1p, share structural and functional similarity with the spinal muscular atrophy-associated proteins SMN and SIP1
The Schizosaccharomyces pombe protein Yab8p and a novel factor, Yip1p, share structural and functional similarity with the spinal muscular atrophy-associated proteins SMN and SIP1
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DOI：
10.1093/hmg/9.5.663
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发表时间：
2000-03-22
影响因子：
3.5
通讯作者：
Fischer, U
中科院分区：
文献类型：
--
作者：
Hannus, S;Bühler, D;Fischer, U
运动神经元疾病脊髓性肌萎缩症 (SMA) 是由运动神经元 (SMN) 蛋白功能存活水平降低引起的。先前的研究表明，SMN 与 SMN 相互作用蛋白 SIP1 结合，并介导剪接体 U snRNP 在细胞质中的组装。此外，最近还提出了 SMN 在前 mRNA 剪接中的核功能。在这里，我们描述了对粟酒裂殖酵母蛋白 Yab8p 的分析，并提供了证据证明它在结构和功能上与高等真核生物中发现的 SMN 相关。我们发现 Yab8p 通过其 N 末端与一种名为 Yip1p 的新型蛋白质相互作用。重要的是，Yip1p 与 SIP1 表现出同源性，并且与 Yab8p 的结合模式与 SMN-SIP1 相互作用非常相似。因此，Yip1p 很可能是粟酒裂殖酵母中 SIP1 的同源物。 Yab8p 和 Yip1p 主要定位于细胞核。遗传学研究表明 Yab8p 对于生存能力至关重要。引人注目的是，在条件敲除菌株中抑制 YAB8 表达会导致 Poly(A) mRNA 核积聚并抑制剪接。这些数据将 Yab8p 确定为参与剪接的新因子，并表明 Yab8p 发挥与 SMN 核库相似或相同的功能。我们的研究提供了一个模型系统来研究酵母中 SMN 的细胞功能，并且应该有助于理解导致 SMA 的分子事件。
The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of functional survival of motor neurons (SMN) protein. Previous studies have shown that SMN binds to the SMN-interacting protein SIP1 and mediates the assembly of spliceosomal U snRNPs in the cytoplasm. In addition, a nuclear function for SMN in pre-mRNA splicing has recently been proposed. Here, we describe the analysis of the Schizosaccharomyces pombe protein Yab8p and provide evidence that it is structurally and functionally related to SMN found in higher eukaryotes. We show that Yab8p interacts via its N-terminus with a novel protein termed Yip1p. Importantly, Yip1p exhibits homology to SIP1, and the mode of binding to Yab8p is remarkably similar to the SMN-SIP1 interaction. Hence, Yip1p is likely to be the homologue of SIP1 in S.pombe. Yab8p and Yip1p localize predominantly in the nucleus. Genetic studies demonstrate that Yab8p is essential for viability. Strikingly, suppression of YAB8 expression in a conditional knock-out strain causes nuclear accumulation of poly(A) mRNA and inhibition of splicing. These data identify Yab8p as a novel factor involved in splicing and suggest that Yab8p exerts a function similar or identical to the nuclear pool of SMN. Our studies provide a model system to study the cellular function of SMN in yeast, and should help in understanding the molecular events leading to SMA.