A number of achievements were selected as the Top Ten Progress in China's Life Sciences in 2021

Mechanism of novel coronavirus escaping host innate immunity and antiviral drugs. Two years into the COVID-19 epidemic, emerging mutant strains pose an urgent need for the development of broad-spectrum drugs. The "transcriptional replication complex" consists of viral replicase, which is responsible for the whole process of viral transcription and replication. It is highly conserved in each mutant strain and is the core target of developing broad-spectrum drugs. The research group of Academician Rao Zihe and Professor Lou Zhiyong of Tsinghua University has discovered and reconstructed the complete composition of the novel coronavirus transcription and replication machine for the first time in the world. On this basis, the key enzyme molecules of viral mRNA "cap" maturation were identified for the first time, which answered the unresolved questions in coronavirus research for nearly 30 years. Moreover, the molecule is highly conserved in various mutant strains and has no homologues in human beings, providing a new target for the development of novel and safe broad-spectrum antiviral drugs. At the same time, they also found for the first time that the virus "removes" the right base and antiviral drugs in a "trans-traceback" way, clarifying the molecular mechanism of the adverse effect of drugs such as Redesivir, and providing a key scientific basis for optimizing antiviral drugs targeting polymerase. These findings are published in the journal Cell, 184(1):184-193; Cell, 184(13):3474-3485).

Transcription initiation supercomplex assembly mechanism. The transcriptional initiation supercomplex is the core of the transcriptional step in the central law, which is of great significance for understanding the regulation of gene expression and related physiological and pathological processes, and has been the core and frontier of international life science research. The team of Xu Yanhui at Fudan University analyzed the three-dimensional structure of the transcription initiation complex PIC and its transcription initiation super complex composed of Mediator (Mediator), systematically demonstrated the whole process of the transcription machine to recognize and complete the assembly of different types of promoters, and revealed why transcription occurs on the promoters of almost all genes. Overturning the traditional understanding of promoter recognition and transcription initiation complex assembly, we elucidate the mechanism of Mediator promoting PIC assembly and transcriptional activation. These results are published in two long papers in the journal Science 372, eaba8490; Science 372, eabg0635), one of which was selected for the cover article in the journal Science, titled "How Transcription Begins."

A new model of high efficiency and low toxicity therapy to improve the curative effect of middle and advanced nasopharyngeal carcinoma. Nasopharyngeal cancer is a tumor with "Chinese characteristics", accounting for half of the new cases in the world. Small residual tumors in the whole body after radiotherapy are the root cause of treatment failure, and due to the poor physical condition of patients after radiotherapy, it is difficult to tolerate the previous high-intensity traditional chemotherapy (the completion rate is only about 40%-50%), which becomes the bottleneck restricting the improvement of curative effect. Ma Jun's research team at the Cancer Prevention and Control Center of Sun Yat-sen University proposed a metronomic chemotherapy mode of small-dose, long-term oral cytotoxic drug capecitabine, which can continuously inhibit tumor through anti-angiogenesis, killing tumor stem cells and other mechanisms, while improving body tolerance. A multi-center, prospective clinical study led by Professor Jun Ma found that the use of "capecitabine beat chemotherapy" after radiotherapy can significantly reduce the risk of failure by 45%, and the incidence of serious side effects is reduced by three-fifths, and the completion rate is 74%. At the same time, the oral use of capecitabine is convenient and easy to promote to the grassroots. Thus, the study broke the bottleneck of the efficacy of traditional chemotherapy and established a new standard for the treatment of nasopharyngeal cancer that is internationally leading, efficient, low toxic and simple. The results are published in the Lancet (2021, 398(10297): 303-313).

Rapid de novo domestication of allotetraploid wild rice. The current cultivated rice is the result of thousands of years of artificial domestication from the ancestral diploid wild rice, accompanied by a decrease in genetic diversity and the loss of excellent genes. A team led by academician Jiayang Li of the Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences first proposed a new strategy for rapid de niviation of allotetraploid wild rice, which provides a new feasible path for coping with future food crises and opens up a new breeding direction. Using this strategy as the blueprint, the project selected a tetraploid tall culm wild rice resource, established an efficient tissue culture regeneration, genetic transformation and gene editing system, assembled a high-quality reference genome, and successfully created a new tetraploid rice material with different types of improved grain setting, awn, plant height, grain length, stalk thickness, growth period, etc., breaking through all technical bottlenecks. It is proved that rapid de novo domestication strategy of allotetraploid wild rice is highly feasible. The successful cultivation of new tetraploid rice crops in the future is expected to bring a subversive revolution to world food production. The results are in the journal Cell (Cell, 2021,184 (5):1156-1170).