A few days ago, Xu Yanhui's team from Shanghai Medical College of Fudan University published a long research article in the journal Science, which for the first time reproduced the 16 continuous dynamic whole processes of transcription from de novo with structure, revealing the molecular mechanism of universal transcription factor (GTFS) and transcription vesicles synergizing with RNA polymerase POL II to regulate the transition from transcription initiation to transcriptional extension.
The picture shows a screenshot of the publication of the article. All articles** are provided by Fudan Shangyi.
The genetic material of life is DNA, and DNA can pass on genetic information along with the cell by replicating itself. DNA can be transcribed to form RNA, and RNA synthesizes proteins through the process of translation.
Transcription is the core of gene expression regulation, which plays an important role in human development and disease occurrence. Gene transcription in eukaryotic cells needs to go through multiple stages such as initiation, extension, and termination. In order to achieve differential gene expression on the basis of the same set of genomes, multicellular organisms need to go through a very complex and delicate gene expression regulation process. Over the past few decades, many laboratories have carried out a lot of exploratory work using biochemistry, single-molecule biophysics, and structural biology methods, but the understanding of the process and molecular mechanism is not deep enough.
Xu's team unraveled an important dynamic event in the transcription process: the transition from transcriptional initiation to transcriptional extension, also known as promoter escape. Promoter escape is a critical transition step in transcription from initiation to extension, during which the conformation of RNA polymerase II needs to change to dissociate generic transcription factors while generating RNA products.
This process has long been shrouded in mystery. Zhu Bing, a researcher at the Institute of Biophysics of the Chinese Academy of Sciences, commented that "revealing the promoter escape process" is a long-term unsolved problem in the field, "because this is a fast dynamic event, the speed of RNA polymerase II extension is generally considered to be thousands of bases per minute, while the promoter escape process involves only the synthesis of the initial 20 bases or so, that is to say, a series of dynamic events need to be completed in a few seconds, which is a great challenge for structural biology research."
According to reports, the Fudan medical team has designed a series of transcription templates that can control any base position of RNA polymerase II when it stops at the first 17 bases of transcription. The design is like turning a coherent scene into a freeze-frame frame, and then the researchers gradually capture each step of the way to form a dynamic "movie." This "film" also depicts for the first time the whole dynamic process of continuous transcription initiation, revealing the complete transcription initiation process and its molecular mechanism.
Previously, Yanhui Xu's team published 5 studies in the journal Science**, revealing the molecular mechanisms of multiple key processes of transcription initiation, including revealing the chromatin remodeling mechanism of the human BAF complex, the transcription initiation complex recognizing gene promoter and its dynamic assembly mechanism, the intermediary promoting RNA polymerase phosphorylation and transcriptional activation mechanism, the +1 nucleosome regulating the molecular mechanism of transcription initiation, and the discovery and identification of a novel transcriptional regulatory complex INTAC. The above work systematically reveals the complex state of key points at each stage of transcription initiation, and promotes a deeper understanding of transcription mechanisms.
Chen Xizi, a young researcher at the School of Life Sciences, Fudan University, Liu Weida, a 2019 direct doctoral student from the Institute of Biomedical Sciences of Fudan University, Wang Qianmin, a young researcher, and Wang Xinxin, a postdoctoral fellow at the Guangdong-Hong Kong-Macao Greater Bay Area Institute of Precision Medicine, are the co-first authors of this paper, and Xu Yanhui, a researcher at the Affiliated Cancer Hospital of Fudan University and a part-time researcher at the Institute of Biomedical Sciences, is the corresponding author.
*: China Youth Daily client.