In the long journey of scientific research, behind every achievement lies endless dedication and challenges. Under the leadership of researcher Zhang Yu, the research team from the Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, has persevered for years and finally published remarkable papers in two top international journals “Cell” and “Nature,” bearing witness to their tireless efforts and courage to explore the unknown.
For over a decade, the research team has been committed to deeply analyzing the nucleus and organelles of bacteriophages, bacteria, yeast, and plant cells, revealing the significant role of transcription in key biological mechanisms such as gene expression and DNA repair. Their persistent explorations year after year have enabled them to publish high-impact research papers in top journals like CNS (Cell, Nature, Science).
Researcher Zhang Yu encourages colleagues to dig deep wells on the path of basic research, to focus on their fields, strive for excellence, and tirelessly work to deepen the research in specific scientific areas.
On March 1 of this year, the journal “Cell” published two groundbreaking papers online, focusing on the research of chloroplast gene transcription mechanisms. It is truly an achievement for the papers written by Chinese scientists to be featured as cover articles. Zhang Yu’s team, in collaboration with Associate Professor Zhou Fei from Huazhong Agricultural University and her team, completed the electron microscopy structural analysis of the tobacco chloroplast RNA polymerase complex, aiming to reveal the molecular structure, subunit assembly, and adaptive evolution of the chloroplast gene transcription machinery.
“Of the nine RNA polymerases of great interest in biological cells, the detailed structure and functional mechanism of the chloroplast RNA polymerase have long been unclear, it’s like the missing piece of a jigsaw puzzle,” said Zhang Yu.
On March 28, in the journal “Nature,” Zhang Yu’s team further published a study on the unique structure of the mRNA transcription termination state in yeast cells, which clearly revealed the molecular mechanism of the nuclease mediating mRNA transcription termination, crucial for understanding the overall mechanism of gene transcription.
“If DNA is likened to the hard drive storing information, then genetic information is like data, neatly arranged in different regions of DNA. RNA polymerase transcribes these pieces of information following instructions. However, if the transcription of a piece of genetic information does not properly end, it can interfere with the expression of downstream genes, thereby affecting the stability of the entire genome,” analyzed Zhang Yu further.
In the central dogma of biology, which describes the transcription and translation of genetic information—how DNA is transcribed into RNA and then translated into proteins. Although research on the first two steps—initiation and elongation—has been quite thorough, the termination step has been of little concern, despite its significant scientific value.
For the mechanism of transcription termination, although multiple theoretical models have been proposed by scholars, controversies in this field still exist. Zeng Yuan, a researcher in Zhang Yu’s team, pointed out that the controversy over transcription termination mechanisms might be due to the high complexity involved in such research and the multiple challenges faced during the research process, which leads to fewer researchers venturing into this field. Transcription termination is a rapidly changing dynamic process, occurring and disappearing very swiftly, making it difficult to effectively capture. In addition, polymerase, as a complex that initiates transcription, depends on the collective action of several proteins, which also results in its inherent instability and increases the difficulty of research.
However, studying transcription termination is extremely important. Thorough understanding of the transcription mechanism would allow for better control over gene expression, which in turn would enable more precise design of genetic circuits and gene expression control in the field of synthetic biology. For example, some diseases may be associated with abnormal gene transcription termination, and revealing the mechanisms of transcription termination could aid in the diagnosis and treatment of such diseases.
Zeng Yuan explained that in the process of studying the transcription termination mechanism, their team faced numerous challenges. Despite having identified the research direction in 2020, the experimental process was not smooth. A highlight of the study was the successful acquisition of a specific polymerase complex. The team members, who were initially excited to obtain this complex, soon encountered a new problem: the structure had low resolution and did not allow observation of the required fine details. To address this issue, the research team creatively improved the stability of the complex by adding another protein.
After obtaining a stable polymerase complex, the team members also needed to experimentally demonstrate that this complex structure had terminating activity, in order to confirm the effectiveness of their research model. Zeng Yuan made multiple trips between Shanghai and Beijing to collect experimental data using cryo-electron microscopy, even having to head to Beijing ahead of schedule during a typhoon. The results were disappointing due to sample issues, forcing Zeng Yuan and her colleagues to rapidly adjust the experimental plan.
Zeng Yuan recalled that during this research process, a series of experiments, including one on transcription termination proteins, caused a great deal of trouble for the team. The transcription termination activity of this protein had always been low in the experiments, until June 2023 when Zeng Yuan discovered in the latest literature that researchers had identified a relatively conserved sequence downstream of the gene. Conserved sequences refer to similar sequence segments between different genes that share commonalities. Based on this discovery, the research team applied this conserved sequence to a new experimental system and finally proved the genuine transcription termination activity of the polymerase complex in this system. After a long period of experimental verification and reflection, they eventually provided a reasonable explanation for this transcription termination model.
In the long journey of scientific research, Zhang Yu’s team attained remarkable achievements with their extraordinary perseverance and focus, publishing papers in two top-tier scientific journals within a span of just over 20 days, reflecting their persistent efforts over the years. These two papers were related to the transcription mechanism of chloroplast genes, a field they had been dedicated to for a full 8 years. Likewise, their research on the mRNA transcription termination mechanism in yeast cells is the result of more than 5 years of concentrated effort.
Zhang Yu has his own philosophy of scientific research: “To truly concentrate on a field, it’s a bit like digging a well. Don’t always dig behind others, nor should you stop shallowly after digging multiple ‘shallow wells’. Only by finding the right place and persisting in digging can satisfactory results be obtained.” This statement profoundly reveals the importance of in-depth study and focus on a single scientific question.
Under the guidance of such philosophy, Zhang Yu’s team has achieved remarkable results and witnessed the steadfastness and perseverance in their scientific research path.
