Shi Yigong first revealed the mechanism of LSM protein specific recognition in nature

According to Tsinghua news network, on November 17, Professor Shi Yigong's research group, School of life, Tsinghua University, published online the title of crystal structures of the LSM complex bound to the 3 'end sequence of U6 small nuclear RNA (LSM protein complex binding U6 small nuclear RNA) in the international top academic journal Nature In this paper, we first reported the self-assembled crystal structure of lsm2-8 protein complex and the molecular mechanism of recognizing the 3 'terminal sequence of U6 microRNA Zhou Lijun, Ph.D student, School of life, Tsinghua University, and hang Jing, Ph.D student, medical college, were the co authors of the paper   Here is the specific recognition of lsm2-8 complex with U6 RNA   In eukaryotes, the maturation of messenger RNA performing translation function needs to undergo a very complex process of cutting and splicing in the nucleus This process is mainly carried out by a huge molecular machine (splice some) composed of five small nuclear ribonucleoproteins (snRNP) and a series of auxiliary proteins Each snRNP consists of a small nuclear RNA and a seven membered ring protein complex specifically bound to it Most of the seven membered ring complexes are SM protein hepolymers, and only in U6 small nuclear ribonucleoprotein are LSM protein hepolymers There are more than ten members of LSM protein family, which are highly conserved in various species and participate in various signal pathways related to RNA metabolism In eukaryotic cells, the protein complex of U6 small nuclear ribonucleoprotein is lsm2 / 3 / 4 / 5 / 6 / 7 / 8 It can specifically recognize the 3 'terminal sequence of U6 RNA, and help the interaction between U6 RNA and other members of the cutter, catalyzing the splicing process of RNA In this research paper, Shi Yigong's research group obtained a self-assembled LSM protein complex with good homogeneity and stability through special protein expression means, which overcame the potential denaturation hazard caused by traditional LSM protein extraction methods On the basis of this, the co crystallization of protein complex and RNA fragment was carried out, and the molecular mechanism of lsm2-8 heptamer protein complex specific recognition of U6 snRNA terminal was revealed by means of structural biology and biochemistry analysis Lsm4 / 8 / 2 / 3, the four subunits of lsm2-8 protein complex, uses two conserved sequence patterns to specifically anchor the four uracil at the 3 'end of U6 RNA in the middle cavity formed by the heptator ring, where lsm3 recognizes the last uracil nucleotide Interestingly, when the nucleotide is removed, lsm3 and its similar recognition pattern can anchor the last uracil, causing the whole binding sequence to move backward Except that lsm7, which is adjacent to lsm4, contributes a weak hydrogen bond to RNA binding, the other two subunits are not directly involved in RNA recognition This new creative discovery for the first time describes and explains the "terminal recognition" pattern of US6 RNA by LSM protein from the perspective of three-dimensional crystal structure Because of the dynamic complexity of splicing pathway, scientists are still struggling to explore the mystery of gene splicing since the discovery of gene splicing was awarded the Nobel Prize in physiology and medicine in 1993 The completion of this project has overcome the problem of interest of many research groups in the world, and expressed and crystallized 7 different proteins together For this purpose, new design ideas and research methods are provided The crystal structure analysis of LSM protein complex is the first significant progress made by Shi Yigong research group in RNA splicing pathway, which lays a solid theoretical foundation for better understanding the functional realization of eukaryotic splicing body and revealing the basic principles of life phenomena (editor Zou Changshen)