Athma A. Pai研究团队揭示了mRNA的起始和终止在空间上是协调的。相关论文于2025年10月9日发表在《科学》杂志上。

通过系统地分析转录起始位点和结束位点的联合图谱，该研究团队发现mRNA的上游起始位点优先于上游末端位点，下游位点的图谱也类似地偶联。他们的研究结果表明，一个位置起始终止轴（PITA），其中替代末端位点的图像是基于它们的基因组顺序耦合的。PITA富含具有不同染色质特征的较长基因。该课题组人员发现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。他们的研究结果表明，空间组织和转录动力学将转录起始和mRNA 3 ’端决定耦合在一起，从而定义mRNA异构体的表达。

研究人员表示，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。

附：英文原文

Title: mRNA initiation and termination are spatially coordinated

Author: 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

Issue&Volume: 2025-10-09

Abstract: 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.

DOI: ado8279

Source: https://www.science.org/doi/10.1126/science.ado8279