On the morning of March 6, 2023, the third session of the 2023 Microcosmic Exploration for Scientific Insight—Graduate Student Specialized Course Academic Forum was successfully launched. Yu Zhang, a researcher from the Center for Excellence in Molecular Plant Science of the Chinese Academy of Sciences, was invited to participate in the “Microcosmic Exploration for Scientific Insight—Graduate Student Specialized Course” graduate academic forum and gave an academic report entitled “How Bacterial RNA Polymerase Starts and Brakes”. The report was presided over by Professor Dalei Wu of the Institute of Microbiology Technology, and about 180 teachers and students listened to the report.

Transcription is the process by which RNA polymerase (RNA Polymerase; RNAP) transfers genetic information from DNA to RNA, and it is a key link in the central dogma of molecular biology. Transcription regulation is a decisive factor in the differential expression of genes, determining almost all cellular activities in organisms ranging from unicellular organisms to higher plants and animals. Therefore, elucidating the three-dimensional structure, working mechanism, and regulatory methods of RNAP has always been a frontier field in life sciences.

Prof. Yu Zhang’s research group focuses on the RNAP molecular machinery of single and multiple subunits to explore the regulatory mechanism of transcription, and at the same time develops new antibiotics targeting RNA polymerase in bacteria, and combines biochemistry, structural biology and microbiology to study the following aspects: 1. Molecular mechanism of transcription initiation of bacterial RNA polymerase. 2. Molecular mechanisms of transcription initiation factors regulating bacterial transcription. 3. Molecular Mechanisms of the Association between Bacterial Transcription and DNA Repair. 4. Molecular Mechanisms of Transcriptional Termination of Bacterial RNA Polymerase. 5. Mining and Mechanism of Novel RNA Polymerase Transcriptional Regulatory Proteins. 6. A novel antibiotic targeting bacterial RNA polymerase.

In this academic forum, Professor Yu Zhang took the discovery process of RNA polymerase as the starting point and introduced the process and history of RNA polymerase exploration. When RNA polymerase transcribes to the “stop sequence”, it needs to “brake” from the state of high-speed extension to stop transcription and release RNA. The metaphor is appropriate, in-depth and in-depth, and it is very beneficial. Subsequently, Professor Yu Zhang introduced the scientific research direction of the research group in detail: the study of how bacterial RNA polymerase initiates and terminates transcription. The genetic information in the genome is expressed, which requires RNA polymerase for transcription. The transcription process of synthesizing RNA using DNA as a template is not only the first step in gene expression, but also the main regulatory step in gene expression. Therefore, the study of the molecular structure, operation mechanism and regulatory mechanism of RNA polymerase can answer the basic biological questions of precise regulation of gene expression.

Through ingenious design and improvement, Prof. Yu Zhang’s team captured a series of intermediate states of transcriptional termination of RNA polymerase, and analyzed the three-dimensional structure of RNA polymerase in the intermediate state of transcriptional termination. The polyuridine of the “transcriptional termination sequence” “brakes” the RNA polymerase, immobilizing it in a transcriptional pause, and then the RNA hairpin folds into the RNA polymerase, prompting the RNA to dissociate from the RNA polymerase. The study answers basic scientific questions about gene expression and expands the understanding of the mechanisms of gene expression.

In the course of the lecture, Professor Yu Zhang said to everyone present, “From the development history of RNA polymerase, we can see that in the process of doing scientific research, even if your work results are published by others, do not be discouraged, even if others publish CNS-level articles, even if they win the Nobel Prize, He can also be wrong, as long as you keep doing it, you will be remembered by history.” These words were deafening and injected full of positive energy into the students present.

The lecture was rich in content and sufficient data, and in the interactive session after the report, the teachers and students who participated in the lecture actively asked Mr. Zhang questions about the content of the report, and Mr. Zhang answered everyone’s questions enthusiastically and meticulously. The students said that they benefited a lot from this report.

Prof. Yu Zhang, graduated from Fudan University with a bachelor’s degree and a Ph.D. degree from Shanghai Institute of Materia Medica, Chinese Academy of Sciences. The main research direction of the research group is gene transcription and regulation mechanism, and the working mechanism and activity regulation mechanism of bacterial RNA polymerase are systematically explored. In recent years, our research group has published articles in Science, Nature, Nat. Chem Biol, Nat. Commun, PNAS. eLife, NAR and other academic journals. He was awarded the title of National Outstanding Youth Fund of the National Foundation of the National Science and Technology Foundation of China and Shanghai Young Science and Technology Talent.