The new mystery of gene regulation and disease is revealed

The new mystery of gene regulation and disease is revealed

November 13, 2018 Source: Health News Author: Li Zhe

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How does the regulation of gene expression participate in the development of organisms and affect human health? This is the subject of research by scientists from various countries. Recently, a study by Professor Long Jiafu, a team of the State Key Laboratory of Medicinal Chemistry Biology, School of Life Sciences, Nankai University, revealed the mystery of an important protein complex that affects gene expression regulation, the assembly and functional regulation of the Paf1 complex. This finding lays the molecular foundation for the treatment and drug development of related tumors. Recently, related papers were published online in the internationally renowned academic journal Nature Communication.

During yeast fermentation, plant flowering, fertilized egg development and human life, the gene expression in cells is in an orderly state in time and space, and responds to changes in environmental conditions in a timely manner. Gene transcription elongation is a highly ordered and extremely complex regulatory process in which cells regulate gene expression. The highly conserved polymerase II-related factor 1 complex (Paf1 complex) in eukaryotes plays an important role in regulating gene transcription elongation and chromatin modification. In addition, the Paf1 complex plays a role in many biological processes such as cell cycle regulation, stem cell pluripotency maintenance, DNA repair and signal transduction.

"The Paf1 complex consists of five protein subunits that act as an assistant in the transcription of RNA polymerase II and are involved in the methylation modification of histones in chromatin," Long said. Five protein subunits constitute a complete complex that functions in intracellular transcriptional elongation, in which any two or more protein subunits are grouped together as a subcomplex, while Paf1 and Ctr9 are Paf1 complexes. Two important protein subunits. Many diseases occur and are caused by related genetic mutations. Mutations in Paf1 and Ctr9 can also lead to the development of related diseases.

The Longjiafu team comprehensively utilized the multidisciplinary methods and methods of biochemistry, structural biology and cell biology, and simultaneously analyzed the crystal structure of the human and yeast source Paf1-Ctr9 subcomplex. The study found that the Paf1-Ctr9 subcomplex is important for the assembly of the entire Paf1 complex, revealing the molecular basis of the related tumors caused by mutations in the Paf1 and Ctr9 genes, as well as the histone methylation modification and yeast viability. Important role. "Analyze the crystal structure of the Paf1-Ctr9 subcomplex, and see the fine structure and conformation of these two proteins at the atomic level. The structure of human and yeast sources can also explain the mechanism of action of Paf1 complex in transcriptional elongation. A deeper understanding of the molecular mechanisms underlying transcriptional elongation from lower eukaryotes such as yeast to higher mammals such as human Paf1 complexes is quite conservative," Long said.

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