• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

酵母 U1 snRNP 的选择性人源化导致芽殖酵母中前体 mRNA 剪接的全局抑制和线粒体功能障碍。

Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast.

机构信息

Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA.

Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.

出版信息

RNA. 2024 Jul 16;30(8):1070-1088. doi: 10.1261/rna.079917.123.

DOI:10.1261/rna.079917.123
PMID:38688558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11251525/
Abstract

The recognition of the 5' splice site (5' ss) is one of the earliest steps of pre-mRNA splicing. To better understand, the mechanism and regulation of 5' ss recognition, we selectively humanized components of the yeast U1 (yU1) snRNP to reveal the function of these components in 5' ss recognition and splicing. We targeted U1C and Luc7, two proteins that interact with and stabilize the yU1 snRNA and the 5' ss RNA duplex. We replaced the zinc-finger (ZnF) domain of yeast U1C (yU1C) with its human counterpart, which resulted in a cold-sensitive growth phenotype and moderate splicing defects. We next added an auxin-inducible degron to yeast Luc7 (yLuc7) protein (to mimic the lack of Luc7Ls in human U1 snRNP). We found that Luc7-depleted yU1 snRNP resulted in the concomitant loss of Prp40 and Snu71 (two other essential yU1 snRNP proteins), and further biochemical analyses suggest a model of how these three proteins interact with each other in the U1 snRNP. The loss of these proteins resulted in a significant growth retardation accompanied by a global suppression of pre-mRNA splicing. The splicing suppression led to mitochondrial dysfunction as revealed by a release of Fe into the growth medium and an induction of mitochondrial reactive oxygen species. Together, these observations indicate that the human U1C ZnF can substitute that of yeast, Luc7 is essential for the incorporation of the Luc7-Prp40-Snu71 trimer into yU1 snRNP, and splicing plays a major role in the regulation of mitochondrial function in yeast.

摘要

5' 剪接位点（5' ss）的识别是前体 mRNA 剪接的最早步骤之一。为了更好地理解 5' ss 识别的机制和调控，我们选择性地将酵母 U1（yU1）snRNP 的成分人源化，以揭示这些成分在 5' ss 识别和剪接中的功能。我们针对与 yU1 snRNA 和 5' ss RNA 双链相互作用并稳定其结构的两种蛋白 U1C 和 Luc7 进行了靶向研究。我们用其人类对应物替换了酵母 U1C（yU1C）的锌指（ZnF）结构域，导致其表现出冷敏感生长表型和中度剪接缺陷。接下来，我们在酵母 Luc7（yLuc7）蛋白中添加了一个植物生长素诱导的降解结构域（以模拟人类 U1 snRNP 中缺乏 Luc7Ls）。我们发现，Luc7 缺失的 yU1 snRNP 导致 Prp40 和 Snu71（另外两种必需的 yU1 snRNP 蛋白）同时丢失，进一步的生化分析提出了这三种蛋白在 U1 snRNP 中相互作用的模型。这些蛋白的丢失导致生长明显迟缓，并伴有前体 mRNA 剪接的全面抑制。剪接抑制导致线粒体功能障碍，表现在生长介质中 Fe 的释放和线粒体活性氧的诱导。总之，这些观察结果表明，人源 U1C ZnF 可以替代酵母的，Luc7 对于 Luc7-Prp40-Snu71 三聚体掺入 yU1 snRNP 是必需的，剪接在酵母中线粒体功能的调控中起着主要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/d03522d601bb/1070f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/379c16a1096d/1070f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/f8c1b5a1ae9a/1070f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/963967459332/1070f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/e54176b53190/1070f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/c4ae0ab2132f/1070f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/21e90d196867/1070f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/2b29b4309058/1070f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/d03522d601bb/1070f08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/379c16a1096d/1070f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/f8c1b5a1ae9a/1070f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/963967459332/1070f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/e54176b53190/1070f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/c4ae0ab2132f/1070f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/21e90d196867/1070f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/2b29b4309058/1070f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c8/11251525/d03522d601bb/1070f08.jpg

相似文献

1
Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast.酵母 U1 snRNP 的选择性人源化导致芽殖酵母中前体 mRNA 剪接的全局抑制和线粒体功能障碍。
RNA. 2024 Jul 16;30(8):1070-1088. doi: 10.1261/rna.079917.123.
2
Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast.酵母U1 snRNP的特定人源化导致芽殖酵母中前体mRNA剪接的整体抑制和线粒体功能障碍。
bioRxiv. 2023 Dec 15:2023.12.15.571893. doi: 10.1101/2023.12.15.571893.
3
Functional analysis of the zinc finger modules of the splicing factor Luc7.Luc7 剪接因子锌指模块的功能分析。
RNA. 2024 Jul 16;30(8):1058-1069. doi: 10.1261/rna.079956.124.
4
Swt21p Is Required for Nam8p-U1 snRNP Association and Efficient Pre-mRNA Splicing in .Swt21p是Nam8p与U1 snRNP结合以及酿酒酵母中高效前体mRNA剪接所必需的。
Int J Mol Sci. 2025 Jun 6;26(12):5440. doi: 10.3390/ijms26125440.
5
Cells resist starvation through a nutrient stress splice switch.细胞通过营养应激剪接开关来抵抗饥饿。
Nucleic Acids Res. 2025 Jun 20;53(12). doi: 10.1093/nar/gkaf525.
6
Structure-function analysis and genetic interactions of the Luc7 subunit of the Saccharomyces cerevisiae U1 snRNP.酿酒酵母U1 snRNP的Luc7亚基的结构-功能分析及遗传相互作用
RNA. 2016 Sep;22(9):1302-10. doi: 10.1261/rna.056911.116. Epub 2016 Jun 27.
7
The U1 snRNP-specific protein U1C is a key regulator of SMN complex-mediated snRNP formation.U1 snRNP特异性蛋白U1C是SMN复合物介导的snRNP形成的关键调节因子。
J Biol Chem. 2025 Jul 22;301(9):110514. doi: 10.1016/j.jbc.2025.110514.
8
CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into alternative splicing.酿酒酵母 U1 snRNP 的冷冻电镜结构为选择性剪接提供了新视角。
Nat Commun. 2017 Oct 19;8(1):1035. doi: 10.1038/s41467-017-01241-9.
9
The FF domains of yeast U1 snRNP protein Prp40 mediate interactions with Luc7 and Snu71.酵母U1 snRNP蛋白Prp40的FF结构域介导与Luc7和Snu71的相互作用。
BMC Biochem. 2008 Nov 11;9:29. doi: 10.1186/1471-2091-9-29.
10
Luc7p, a novel yeast U1 snRNP protein with a role in 5' splice site recognition.Luc7p，一种在5'剪接位点识别中起作用的新型酵母U1 snRNP蛋白。
Genes Dev. 1999 Sep 15;13(18):2425-38. doi: 10.1101/gad.13.18.2425.

引用本文的文献

1
Cells resist starvation through a nutrient stress splice switch.细胞通过营养应激剪接开关来抵抗饥饿。
Nucleic Acids Res. 2025 Jun 20;53(12). doi: 10.1093/nar/gkaf525.
2
Functional analysis of the zinc finger modules of the splicing factor Luc7.Luc7 剪接因子锌指模块的功能分析。
RNA. 2024 Jul 16;30(8):1058-1069. doi: 10.1261/rna.079956.124.
3
Functional Analysis of the Zinc Finger Modules of the Splicing Factor Luc7.剪接因子Luc7锌指模块的功能分析

本文引用的文献

1
Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain.在人源化酵母菌株中，各个内含子对剪接抑制剂的反应存在广泛差异。
RNA. 2024 Jan 16;30(2):149-170. doi: 10.1261/rna.079866.123.
2
Introns: the "dark matter" of the eukaryotic genome.内含子：真核生物基因组的“暗物质”。
Front Genet. 2023 May 16;14:1150212. doi: 10.3389/fgene.2023.1150212. eCollection 2023.
3
The problem of selection bias in studies of pre-mRNA splicing.研究前体 mRNA 剪接中选择偏差的问题。
bioRxiv. 2024 Feb 4:2024.02.04.578419. doi: 10.1101/2024.02.04.578419.
Nat Commun. 2023 Apr 8;14(1):1966. doi: 10.1038/s41467-023-37650-2.
4
U1 snRNP increases RNA Pol II elongation rate to enable synthesis of long genes.U1 snRNP 提高 RNA Pol II 延伸速度，从而促进长基因的合成。
Mol Cell. 2023 Apr 20;83(8):1264-1279.e10. doi: 10.1016/j.molcel.2023.03.002. Epub 2023 Mar 24.
5
Full humanization of the glycolytic pathway in Saccharomyces cerevisiae.在酿酒酵母中完全实现糖酵解途径的人源化。
Cell Rep. 2022 Jun 28;39(13):111010. doi: 10.1016/j.celrep.2022.111010.
6
Intron-mediated induction of phenotypic heterogeneity.内含子介导的表型异质性诱导。
Nature. 2022 May;605(7908):113-118. doi: 10.1038/s41586-022-04633-0. Epub 2022 Apr 20.
7
Autosomal dominant optic atrophy: A novel treatment for splice defects using U1 snRNA adaption.常染色体显性遗传性视神经萎缩：一种使用U1小核核糖核酸适配体治疗剪接缺陷的新方法。
Mol Ther Nucleic Acids. 2021 Oct 21;26:1186-1197. doi: 10.1016/j.omtn.2021.10.019. eCollection 2021 Dec 3.
8
Total RNA Extraction from Using Hot Acid Phenol.使用热酸性苯酚从……中提取总RNA。 （原句“from”后缺少具体内容）
Cold Spring Harb Protoc. 2021 Dec 1;2021(12):2021/12/pdb.prot101691. doi: 10.1101/pdb.prot101691.
9
Selective functional inhibition of a tumor-derived p53 mutant by cytosolic chaperones identified using split-YFP in budding yeast.利用芽殖酵母中的分裂 YFP 技术鉴定细胞溶质伴侣对肿瘤衍生 p53 突变体的选择性功能抑制作用。
G3 (Bethesda). 2021 Sep 6;11(9). doi: 10.1093/g3journal/jkab230.
10
Structural insights into how Prp5 proofreads the pre-mRNA branch site.结构洞察 Prp5 如何校对前 mRNA 分支位点。
Nature. 2021 Aug;596(7871):296-300. doi: 10.1038/s41586-021-03789-5. Epub 2021 Aug 4.