瑞典卡洛琳斯卡研究所Rickard Sandberg课题组发现，单细胞新RNA测序揭示新型转录原则。2024年8月28日，国际知名学术期刊《自然—细胞生物学》在线发表了这一成果。

研究人员对1万枚单个原代小鼠成纤维细胞中新转录的RNA（标记为4-硫脲嘧啶）进行了分析，以更广泛地推断突发动力学和协调性。研究人员展示了从新RNA谱中推断出的数据能够分离出共同决定突发大小的动力学参数，并且是合成速率（而非转录关闭速率）控制着突发大小。

重要的是，转录开启和关闭速率的全基因组推断提供了RNA聚合酶II以突发形式转录基因的确凿证据。尽管最近的报道确实识别了转录共爆发的例子，但尚未进行全面的分析。研究人员通过等位基因分辨率生成的深度新RNA谱显示，除了某些基因对（特别是位于基因组接近区域的同源基因）外，共爆发的出现频率并不比偶然发生的频率高。因此，新RNA单细胞分析极大地改进了对转录突发的推断，并为哺乳动物基因的独立转录爆发提供了有力证据。

据悉，从单细胞RNA测序数据中对转录爆发的分析揭示了可以推断的动力学参数的变化和调控模式。

附：英文原文

Title: Single-cell new RNA sequencing reveals principles of transcription at the resolution of individual bursts

Author: Ramskld, Daniel, Hendriks, Gert-Jan, Larsson, Anton J. M., Mayr, Juliane V., Ziegenhain, Christoph, Hagemann-Jensen, Michael, Hartmanis, Leonard, Sandberg, Rickard

Issue&Volume: 2024-08-28

Abstract: Analyses of transcriptional bursting from single-cell RNA-sequencing data have revealed patterns of variation and regulation in the kinetic parameters that could be inferred. Here we profiled newly transcribed (4-thiouridine-labelled) RNA across 10,000 individual primary mouse fibroblasts to more broadly infer bursting kinetics and coordination. We demonstrate that inference from new RNA profiles could separate the kinetic parameters that together specify the burst size, and that the synthesis rate (and not the transcriptional off rate) controls the burst size. Importantly, transcriptome-wide inference of transcriptional on and off rates provided conclusive evidence that RNA polymerase II transcribes genes in bursts. Recent reports identified examples of transcriptional co-bursting, yet no global analyses have been performed. The deep new RNA profiles we generated with allelic resolution demonstrated that co-bursting rarely appears more frequently than expected by chance, except for certain gene pairs, notably paralogues located in close genomic proximity. Altogether, new RNA single-cell profiling critically improves the inference of transcriptional bursting and provides strong evidence for independent transcriptional bursting of mammalian genes.

DOI: 10.1038/s41556-024-01486-9

Source: https://www.nature.com/articles/s41556-024-01486-9