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首页> 外文期刊>Molecular and Cellular Biology >Cwc23, an Essential J Protein Critical for Pre-mRNA Splicing with a Dispensable J Domain
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Cwc23, an Essential J Protein Critical for Pre-mRNA Splicing with a Dispensable J Domain

机译：Cwc23，是必需的J蛋白，对于前mRNA剪接具有可有可无的J结构域至关重要

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摘要

J proteins are structurally diverse, obligatory cochaperones of Hsp70s, each with a highly conserved J domain that plays a critical role in the stimulation of Hsp70's ATPase activity. The essential protein, Cwc23, is one of 13 J proteins found in the cytosol and/or nucleus of Saccharomyces cerevisiae. We report that a partial loss-of-function CWC23 mutant has severe, global defects in pre-mRNA splicing. This mutation leads to accumulation of the excised, lariat form of the intron, as well as unspliced pre-mRNA, suggesting a role for Cwc23 in spliceosome disassembly. Such a role is further supported by the observation that this mutation results in reduced interaction between Cwc23 and Ntr1 (SPP382), a known component of the disassembly pathway. However, Cwc23 is a very atypical J protein. Its J domain, although functional, is dispensable for both cell viability and pre-mRNA splicing. Nevertheless, strong genetic interactions were uncovered between point mutations encoding alterations in Cwc23's J domain and either Ntr1 or Prp43, a DExD/H-box helicase essential for spliceosome disassembly. These genetic interactions suggest that Hsp70-based chaperone machinery does play a role in the disassembly process. Cwc23 provides a unique example of a J protein; its partnership with Hsp70 plays an auxiliary, rather than a central, role in its essential cellular function.
机译：J蛋白是Hsp70s的结构多样性，强制性伴侣蛋白，每个蛋白均具有高度保守的J结构域，在刺激Hsp70的ATPase活性中起着至关重要的作用。必需蛋白Cwc23是在啤酒酵母（Saccharomyces cerevisiae）的细胞质和/或细胞核中发现的13种J蛋白之一。我们报告，部分功能丧失的 CWC23 突变体在pre-mRNA剪接中具有严重的全局缺陷。此突变导致内含子的切下，套索形式以及未剪接的pre-mRNA的积累，提示Cwc23在剪接体拆卸中的作用。观察到这种突变进一步降低了Cwc23与Ntr1（ SPP382 ）之间的相互作用，这一发现进一步支持了这种作用，Ntr1是拆卸途径的已知成分。但是，Cwc23是非常不典型的J蛋白。其J结构域虽然具有功能，但对于细胞活力和mRNA前剪接都是必不可少的。然而，在编码Cwc23的J结构域与Ntr1或Prp43的点突变之间未发现强烈的遗传相互作用，Ntr1或Prp43是剪接体拆卸必不可少的DExD / H-box解旋酶。这些遗传相互作用表明，基于Hsp70的分子伴侣机制确实在拆卸过程中起作用。 Cwc23提供了J蛋白的独特例子;它与Hsp70的伙伴关系在其基本的细胞功能中起着辅助而不是中心的作用。

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