Author of Atomic Resolution Structure of Human Scissors: Shi Igong.

On May 12, 2017, the Shi Igong Research Group of Tsinghua University's School of Life and the Center for High-Sophisticated Innovation in Structural Biology published an online study entitled "An Atomic Structure of Human Spliceosome" entitled "Atomic Scissors".
This is the first high-resolution human-to-human shear structure, and the first to observe the structure of shears from higher organisms other than yeast on a scale of near-atomic resolution, further revealing the assembly and working of the shears and providing an important basis for understanding the RNA cutting process of higher organisms.
most genes are not continuous in the cells of the european nuclei, and their coding regions (exons) are separated by non-coding sequences known as "introns".
in gene expression, the inclusions need to be "cut" and "joined" by two chemical reactions to be removed, allowing the coding regions to be connected to different messenger RNA (mRNA).
the same gene, because the boundaries and numbers of inclusions are different, and when clipped, mRNAs of a variety of encoded proteins can be produced.
RNA scissors are a unique process for all urns, one of the key steps in the "central law" of the true nuclear organisms, and are considered to be an important molecular basis for the complexity of the urn.
RNA cutting process must be highly accurate, and any errors can lead to abnormal gene expression and even disease.
statistics, more than one-third of hereditary diseases are associated with abnormal RNA shearing.
complex physiological process of cutting RNA is performed by spliceosome.
Shear is the most complex large molecular machine known in cells, with a large molecular weight and a highly dynamic composition consisting mainly of protein-nucleic acid-forming complexes (ribonucleoprotein, RNP), which processes identification, assembly, activation, catalysis, etc. on pre-messenger RNA (pre-mRNA), and eventually dissociates into many small functional units after the reaction ends to enter the next reaction cycle.
according to the composition and composition of the shear body, the shear can be divided into E, A, B, Bact, B, C, C, P, ILS and other states (Figure 1).
high-resolution structure of the scissors is essential to understand the structure of the clipping reaction.
In August 2015, Shi's team took the lead in analyzing the high-resolution structure of yeast shears in the world, and in 2016 it reported on the high-resolution structure of yeast shears in different working states, providing the most comprehensive and clear information on the structure of the shears to date, revealing the molecular basis of RNA shearing, and greatly promoting the development of this field.
However, compared with yeast shears, the composition, assembly and regulation of higher organisms represented by humans are more complex, and their structural studies are slow due to the complexity of composition and the instability of the composition.
Since more than one-third of human genetic diseases are directly related to errors in the shearing process, analyzing the structure of human-source shears not only helps to understand the chemical nature of the shear reaction, but also promotes the understanding of the pathogenesis of some diseases and provides the possibility for the development of drugs for the shears.
analysis of human-sourced shears is an extremely important and urgent problem to be solved.
In the latest issue of Cell Research, Shi's team used modified pre-mRNA to assemble human-sourced shears in-body, locking the shear reaction to the state before the first reaction and the second, i.e. the C-state.
Because the human-source shear was so unstable, the researchers used a chemical crosslinker to fix the shear under mild conditions, successfully obtained a stable human-source shear sample, and reconstructed a near-atomic resolution structure of 3.8 E using a single-particle frozen electron mirror (Figures 2 and 3).
in this structure, the core region resolution of the shear body is as high as 3.0-3.5 E, which clearly shows the structure of the catalytic reaction center consisting of more than 20 proteins and RNA (Figure 4).
, they observed that the specific composition of the shear factor closely related to the second step reaction was essential for stabilizing the reaction activity center and catalytic second step transester reaction.
analysis of the structure provides an important structural basis for revealing the structural changes of the shears during the second step of reaction and the identification of the 3 clipping points.
Shi Yigong is the co-author of this article; Zhang Xiaofeng, a ph.D. student at the 15th level of the PTN Project; Yan Entrepreneurship, a distinguished scholar at the Center for High-Sophisticated Innovation in Structural Biology; and Hang Wei, a doctoral student at the Medical College, are co-authors of this paper; Lorenzo I. Finci, a postdoctoral student at the School of Life; and Director of the Frozen Electroscope Platform at Tsinghua University. Lei Jianlin researchers assisted in data collection, platform staff Li Xiaomei, Li Xiaomin in the data collection process to provide help, this topic has been Tsinghua University frozen electroscope platform, high-performance computing platform, the National Protein Facility Experimental Technology Center (Beijing) support, this work mainly received the Beijing Municipal Structural Biology High-sophisticated Innovation Center funding support, and received the National Natural Science Foundation of China and the Ministry of Science and Technology funding.
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