启动子近端剪接位点增强转录。
Promoter proximal splice sites enhance transcription.
作者信息
Furger Andre, O'Sullivan Justin M, Binnie Alexandra, Lee Barbara A, Proudfoot Nick J
机构信息
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
出版信息
Genes Dev. 2002 Nov 1;16(21):2792-9. doi: 10.1101/gad.983602.
Abstract
Reconstruction of a gene with its introns removed results in reduced levels of cytoplasmic mRNA. This is partly explained by introns promoting the export of mRNA through coupling splicing to nuclear export processes. However, we show here that splicing signals can have a direct role in enhancing gene transcription. Removal of promoter proximal splice signals from a mammalian gene or the excision of introns from two different yeast genes results in a marked reduction in levels of nascent transcription, based on both nuclear run-on and direct image analysis. This further establishes that mRNA processing and transcription are tightly coupled mechanisms.
摘要
去除内含子后的基因重建导致细胞质mRNA水平降低。这部分是因为内含子通过将剪接与核输出过程偶联来促进mRNA的输出。然而，我们在此表明剪接信号在增强基因转录方面可发挥直接作用。基于核延伸分析和直接图像分析，从哺乳动物基因中去除启动子近端剪接信号或从两个不同的酵母基因中切除内含子会导致新生转录水平显著降低。这进一步证实mRNA加工和转录是紧密偶联的机制。
相似文献
1
Promoter proximal splice sites enhance transcription.启动子近端剪接位点增强转录。
Genes Dev. 2002 Nov 1;16(21):2792-9. doi: 10.1101/gad.983602.
2
A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo.一个5'剪接位点在体内增强基础转录起始因子的募集。
Mol Cell. 2008 Feb 1;29(2):271-8. doi: 10.1016/j.molcel.2007.11.035.
3
In silico mutagenesis of RNA splicing in HIV-1.人类免疫缺陷病毒1型（HIV-1）RNA剪接的计算机诱变
Biotechnol Bioeng. 2005 Sep 30;91(7):877-93. doi: 10.1002/bit.20560.
4
Differential recruitment of the splicing machinery during transcription predicts genome-wide patterns of mRNA splicing.转录过程中剪接机制的差异募集预测全基因组范围内的mRNA剪接模式。
Mol Cell. 2006 Dec 28;24(6):903-15. doi: 10.1016/j.molcel.2006.12.006.
5
Promoter usage and alternative splicing.启动子使用与可变剪接。
Curr Opin Cell Biol. 2005 Jun;17(3):262-8. doi: 10.1016/j.ceb.2005.04.014.
6
Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene.基因间转录对于抑制酿酒酵母SER3基因是必需的。
Nature. 2004 Jun 3;429(6991):571-4. doi: 10.1038/nature02538.
7
Mutation of the major 5' splice site renders a CMV-driven HIV-1 proviral clone Tat-dependent: connections between transcription and splicing.主要5'剪接位点的突变使巨细胞病毒驱动的HIV-1前病毒克隆依赖于反式激活因子Tat：转录与剪接之间的联系。
FEBS Lett. 2004 Apr 9;563(1-3):113-8. doi: 10.1016/S0014-5793(04)00277-7.
8
Common chromatin architecture, common chromatin remodeling, and common transcription kinetics of Adr1-dependent genes in Saccharomyces cerevisiae.酿酒酵母中Adr1依赖性基因的常见染色质结构、常见染色质重塑和常见转录动力学。
Biochemistry. 2004 Jul 13;43(27):8878-84. doi: 10.1021/bi049577+.
9
The position of yeast snoRNA-coding regions within host introns is essential for their biosynthesis and for efficient splicing of the host pre-mRNA.酵母snoRNA编码区在宿主内含子中的位置对其生物合成以及宿主前体mRNA的有效剪接至关重要。
RNA. 2007 Jan;13(1):138-50. doi: 10.1261/rna.251907. Epub 2006 Nov 29.
10
The control of transcription in Saccharomyces cerevisiae.酿酒酵母中转录的调控。
Bioessays. 1987 Aug;7(2):62-7. doi: 10.1002/bies.950070204.
引用本文的文献
1
U-rich elements drive pervasive cryptic splicing in 3' UTR massively parallel reporter assays.富含尿嘧啶的元件在3'非翻译区大规模平行报告基因检测中驱动广泛的隐蔽剪接。
Nat Commun. 2025 Jul 25;16(1):6844. doi: 10.1038/s41467-025-62000-9.
2
Introns increase gene expression in Caenorhabditis elegans by a mechanism that must be at least partly different than in plants.内含子通过一种机制增加秀丽隐杆线虫中的基因表达，该机制必定至少在一定程度上不同于植物中的机制。
Sci Rep. 2025 May 7;15(1):15862. doi: 10.1038/s41598-025-99739-6.
3
Deletion of splicing factor Cdc5 in Toxoplasma disrupts transcriptome integrity, induces abortive bradyzoite formation, and prevents acute infection in mice.弓形虫中剪接因子Cdc5的缺失破坏了转录组完整性，诱导了流产型缓殖子的形成，并阻止了小鼠的急性感染。
Nat Commun. 2025 Apr 22;16(1):3769. doi: 10.1038/s41467-025-58805-3.
4
A double-agent microRNA regulates viral cross-kingdom infection in animals and plants.一种双功能微小RNA调控动植物中的病毒跨界感染。
EMBO J. 2025 May;44(9):2446-2472. doi: 10.1038/s44318-025-00405-4. Epub 2025 Mar 5.
5
From computational models of the splicing code to regulatory mechanisms and therapeutic implications.从剪接密码的计算模型到调控机制及治疗意义
Nat Rev Genet. 2025 Mar;26(3):171-190. doi: 10.1038/s41576-024-00774-2. Epub 2024 Oct 2.
6
U-rich elements drive pervasive cryptic splicing in 3' UTR massively parallel reporter assays.富含U的元件在3'非翻译区大规模平行报告基因检测中驱动广泛的隐蔽剪接。
bioRxiv. 2024 Aug 5:2024.08.05.606557. doi: 10.1101/2024.08.05.606557.
7
Introns and Their Therapeutic Applications in Biomedical Researches.内含子及其在生物医学研究中的治疗应用。
Iran J Biotechnol. 2023 Oct 1;21(4):e3316. doi: 10.30498/ijb.2023.334488.3316. eCollection 2023 Oct.
8
Examining the capacity of human U1 snRNA variants to facilitate pre-mRNA splicing.检测人类 U1 snRNA 变体促进前体 mRNA 剪接的能力。
RNA. 2024 Feb 16;30(3):271-280. doi: 10.1261/rna.079892.123.
9
Impact on splicing in of random 50-base sequences inserted into an intron.插入内含子的随机 50 个碱基序列对剪接的影响。
RNA. 2023 Dec 18;30(1):52-67. doi: 10.1261/rna.079752.123.
10
α-tubulin regulation by 5' introns in Saccharomyces cerevisiae.α-微管蛋白在酿酒酵母中的 5' 内含子调控。
Genetics. 2023 Dec 6;225(4). doi: 10.1093/genetics/iyad163.
本文引用的文献
1
U1 snRNA associates with TFIIH and regulates transcriptional initiation.U1小核仁核糖核酸与转录因子IIH结合并调节转录起始。
Nat Struct Biol. 2002 Nov;9(11):800-5. doi: 10.1038/nsb862.
2
A conserved mRNA export machinery coupled to pre-mRNA splicing.一种与前体mRNA剪接相关的保守的mRNA输出机制。
Cell. 2002 Feb 22;108(4):523-31. doi: 10.1016/s0092-8674(02)00627-x.
3
Integrating mRNA processing with transcription.将信使核糖核酸加工与转录整合
Cell. 2002 Feb 22;108(4):501-12. doi: 10.1016/s0092-8674(02)00617-7.
4
Stimulatory effect of splicing factors on transcriptional elongation.剪接因子对转录延伸的刺激作用。
Nature. 2001;414(6866):929-33. doi: 10.1038/414929a.
5
RNA ligands generated against complex nuclear targets indicate a role for U1 snRNP in co-ordinating transcription and RNA splicing.针对复杂核靶点产生的RNA配体表明U1 snRNP在协调转录和RNA剪接中发挥作用。
FEBS Lett. 2001 Dec 7;509(2):282-6. doi: 10.1016/s0014-5793(01)03188-x.
6
The retroviruses human immunodeficiency virus type 1 and Moloney murine leukemia virus adopt radically different strategies to regulate promoter-proximal polyadenylation.逆转录病毒1型人类免疫缺陷病毒和莫洛尼鼠白血病病毒采用截然不同的策略来调控启动子近端的多聚腺苷酸化。
J Virol. 2001 Dec;75(23):11735-46. doi: 10.1128/JVI.75.23.11735-11746.2001.
7
Multiple transcript cleavage precedes polymerase release in termination by RNA polymerase II.在RNA聚合酶II终止过程中，多个转录本切割先于聚合酶释放。
Cell. 2001 Jun 1;105(5):669-81. doi: 10.1016/s0092-8674(01)00372-5.
8
Interruption of coding sequences by heterologous introns can enhance the functional expression of recombinant genes.异源内含子对编码序列的打断能够增强重组基因的功能表达。
Gene Ther. 2001 Apr;8(8):649-53. doi: 10.1038/sj.gt.3301440.
9
Gene therapy: trials and tribulations.基因治疗：试验与磨难
Nat Rev Genet. 2000 Nov;1(2):91-9. doi: 10.1038/35038533.
10
Initial sequencing and analysis of the human genome.人类基因组的初步测序与分析。
Nature. 2001 Feb 15;409(6822):860-921. doi: 10.1038/35057062.
Zotero 插件