CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into alternative splicing.

CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into alternative splicing.
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DOI:
10.1038/s41467-017-01241-9
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发表时间:
2017-10-19
影响因子:
16.6
通讯作者:
Zhao R
Zhao R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li X;Liu S;Jiang J;Zhang L;Espinosa S;Hill RC;Hansen KC;Zhou ZH;Zhao R

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U1 snRNP 在 5′-剪接位点识别中发挥着关键作用,并且是替代剪接因子的常见目标。这些因子与人类 U1 snRNP 短暂相关,不适合结构研究,而它们的酿酒酵母(酵母)同源物是 U1 snRNP 的稳定成分。在这里,我们以 3.6 Å 分辨率报告了酵母 U1 snRNP 的冷冻电镜结构,以及 10 个核心蛋白、其 RNA 的几乎所有必需结构域以及 5 个稳定相关的辅助蛋白的原子模型。足形酵母 U1 snRNP 在“球和脚趾”区域包含一个核心,其结构与人类 U1 snRNP 相似。所有辅助蛋白均位于“足弓和足跟”区域,并通过 Prp42/Prp39 旁系同源物连接至核心。我们证明同型二聚体人 PrpF39 直接与 U1C-CTD 相互作用,镜像酵母 Prp42/Prp39,支持酵母 U1 snRNP 作为模型来了解瞬时相关辅助蛋白如何在选择性剪接中招募人 U1 snRNP。 U1 snRNP 对于前 mRNA 剪接中的 5' 剪接位点识别至关重要。在这里,作者描述了酵母 U1 snRNP 的冷冻电镜结构,并提出 PrpF39 是一种替代剪接因子,对于通过其他替代剪接因子成功招募 U1 snRNP 至关重要。
U1 snRNP plays a critical role in 5ʹ-splice site recognition and is a frequent target of alternative splicing factors. These factors transiently associate with human U1 snRNP and are not amenable for structural studies, while their Saccharomyces cerevisiae (yeast) homologs are stable components of U1 snRNP. Here, we report the cryoEM structure of yeast U1 snRNP at 3.6 Å resolution with atomic models for ten core proteins, nearly all essential domains of its RNA, and five stably associated auxiliary proteins. The foot-shaped yeast U1 snRNP contains a core in the “ball-and-toes” region architecturally similar to the human U1 snRNP. All auxiliary proteins are in the “arch-and-heel” region and connected to the core through the Prp42/Prp39 paralogs. Our demonstration that homodimeric human PrpF39 directly interacts with U1C-CTD, mirroring yeast Prp42/Prp39, supports yeast U1 snRNP as a model for understanding how transiently associated auxiliary proteins recruit human U1 snRNP in alternative splicing. U1 snRNP is critical for 5′ splicing site recognition in pre-mRNA splicing. Here the authors describe the cryo-EM structure of the yeast U1 snRNP and suggest that PrpF39 is an alternative splicing factor essential for the successful recruitment of U1 snRNP by other alternative splicing factors.
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影响因子: 2.2
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期刊: Acta crystallographica. Section D, Biological crystallography
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