mRNA的起始和终止在空间上是协调的

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-10-09 DOI:10.1126/science.ado8279

Ezequiel Calvo-Roitberg, Christine L. Carroll, GyeungYun Kim, Valeria Sanabria, Sergey V. Venev, Steven T. Mick, Joseph D. Paquette, Maritere Uriostegui-Arcos, Job Dekker, Ana Fiszbein, Athma A. Pai

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引用次数: 0

摘要

转录起始和终止决定驱动信使RNA （mRNA）异构体多样性，但它们之间的关系仍然知之甚少。通过系统地分析转录起始位点和结束位点的联合使用，我们观察到使用上游起始位点的mRNA优先使用上游末端位点，而下游位点的使用也类似地偶联。我们的研究结果表明，一个位置起始终止轴（PITA），其中使用的替代终端位点是基于他们的基因组顺序耦合。PITA富含具有不同染色质特征的较长基因。我们发现mRNA 5 ‘起始点的选择直接影响3 ’末端，这取决于RNA聚合酶II的转运速度。我们的研究结果表明，空间组织和转录动力学耦合转录起始和mRNA 3 '端决定来定义mRNA异构体的表达。

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mRNA initiation and termination are spatially coordinated

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mRNA initiation and termination are spatially coordinated

Transcriptional initiation and termination decisions drive messenger RNA (mRNA) isoform diversity but the relationship between them remains poorly understood. By systematically profiling joint usage of transcription start and end sites, we observed that mRNA using upstream starts preferentially use upstream end sites and that the usage of downstream sites is similarly coupled. Our results suggest a positional initiation termination axis (PITA), in which usage of alternative terminal sites are coupled based on their genomic order. PITA is enriched in longer genes with distinct chromatin features. We find that mRNA 5′ start choice directly influences 3′ ends depending on RNA polymerase II trafficking speed. Our results indicate that spatial organization and transcriptional dynamics couple transcription initiation and mRNA 3′ end decisions to define mRNA isoform expression.

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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