Laboratory of Cell Biology, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Laboratory of the Biology and Pathology of the Eye, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
PLoS One. 2020 Mar 2;15(3):e0223030. doi: 10.1371/journal.pone.0223030. eCollection 2020.
Numerous studies show that various genes in all kinds of organisms are transcribed discontinuously, i.e. in short bursts or pulses with periods of inactivity between them. But it remains unclear whether ribosomal DNA (rDNA), represented by multiple copies in every cell, is also expressed in such manner. In this work, we synchronized the pol I activity in the populations of tumour derived as well as normal human cells by cold block and release. Our experiments with 5-fluorouridine (FU) and BrUTP confirmed that the nucleolar transcription can be efficiently and reversibly arrested at +4°C. Then using special software for analysis of the microscopic images, we measured the intensity of transcription signal (incorporated FU) in the nucleoli at different time points after the release. We found that the ribosomal genes in the human cells are transcribed discontinuously with periods ranging from 45 min to 75 min. Our data indicate that the dynamics of rDNA transcription follows the undulating pattern, in which the bursts are alternated by periods of rare transcription events.
大量研究表明,各种生物的许多基因都是不连续转录的,即在转录过程中存在短时间的爆发或脉冲,其间存在不活跃期。但核糖体 DNA(rDNA)是否也以这种方式表达,目前仍不清楚。rDNA 在每个细胞中都以多个拷贝存在。在这项工作中,我们通过冷阻断和释放使肿瘤衍生的和正常人类细胞群体中的 pol I 活性同步。我们用 5-氟尿嘧啶核苷(FU)和 BrUTP 进行的实验证实,核仁转录可以在+4°C 时被有效地和可逆地阻断。然后,我们使用特殊的软件来分析显微镜图像,测量释放后不同时间点核仁中转录信号(掺入的 FU)的强度。我们发现,人类细胞中的核糖体基因是不连续转录的,其周期从 45 分钟到 75 分钟不等。我们的数据表明,rDNA 转录的动力学遵循波动模式,其中爆发期被罕见转录事件的时期所交替。