The molecular mechanism of SF3B1 mutations leading to RNA splicing disorder

As a key step in the RNA processing process, the accuracy of RNA splicing is one of the prerequisites for the normal expression of a gene. The disorder of gene expression caused by RNA splicing is an important reason for the occurrence of multiple diseases. In recent years, high-throughput sequencing technology has detected a variety of splicing factor mutations in various tumor cells. These mutations have different effects on RNA splicing, leading to abnormal expression of downstream genes. SF3B1 / Hsh155 are a key factor in the early splicing assembly, and a high frequency mutation occurs in a variety of tumor cells with most significant in patients with myelodysplastic syndrome (MDS) and chronic lymphocytic leukemia (CLL). The studies through recombinant horse proteins have shown that these SF3B1 / Hsh155 mutations can lead to changes in the splicing pattern of specific genes, but its molecular mechanism of RNA splicing is not clear.

Recently, the Shanghai Institute of Plant Physiology and Ecology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and the Charles Query Laboratory of Einstein College of Medicine in the United States have published research papers in the International Journal of Genetics and Development, and the study is titled "SF3B1 / Hsh155 HEAT motif mutations using interaction with the spliceosomal ATPase Prp5, resulting in tangential branch site selectivity in pre-mRNA splicing". According to the high conservativeness of SF3B1 / Hsh155 protein and the advantages of the genetic system of budding yeast, it was found that these SF3B1 / Hsh155 high frequency mutants could only specifically change the accuracy of splice recognition of intron frontal region sequences. The accuracy of the identification of other areas of the child is not affected. This feature is very similar to the mutant phenotype of RNA helicase Prp5, which has been studied by Xu Yongzhen team for a long time.

The results of protein interaction showed that SF3B1 / Hsh155 had a direct interaction with Prp5. Further studies showed that the high frequency mutation of SF3B1 / Hsh155 significantly changed the intensity of its interaction with Prp5. It is important that the change in the intensity of this interaction is closely related to the recognition accuracy of the intron fulcrum region. Subsequent mutant studies have shown that enhancing the interaction of SF3B1 / Hsh155-Prp5 facilitates the formation of early splice complexes and accelerates the dissociation of Prp5. Conversely, weakening the interaction between SF3B1 and Hsh155-Prp5 will prevent early splice complex and inhibit the dissociation of Prp5. This progress not only reveals the molecular mechanism of SF3B1 / Hsh155 high frequency mutation leading to RNA splicing disorder and improved the assembly model of early splicing body, but also provided important clues for the further study of related diseases. Flarebio provides recombinant proteins of good quality such as recombinant TLR2 at reasonable prices.