Roles of alternative splicing in infectious diseases: from hosts, pathogens to their interactions  

作　　者：Mengyuan Lyu Hongli Lai Yili Wang Yanbing Zhou Yi Chen Dongsheng Wu Jie Chen Binwu Ying 

机构地区：[1]Department of Laboratory Medicine,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China [2]Department of Thoracic Surgery and Institute of Thoracic Oncology,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,China

出　　处：《Chinese Medical Journal》2023年第7期767-779,共13页中华医学杂志（英文版）

基　　金：National Natural Science Foundation of China(No.82272416)

摘　　要：Alternative splicing(AS)is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs(mRNAs),extremely improving the richness of transcriptome and proteome.Both mammal hosts and pathogens require AS to maintain their life activities,and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS.Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA(named cis-splicing).Parasites also use spliceosomes to splice,but this splicing can occur among different mRNAs(named trans-splicing).Bacteria and viruses directly hijack the host’s splicing machinery to accomplish this process.Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators(abundance,modification,distribution,movement speed,and conformation),which further radiate to alterations in the global splicing profiles.Genes with splicing changes are enriched in immune-,growth-,or metabolism-related pathways,highlighting approaches through which hosts crosstalk with pathogens.Based on these infection-specific regulators or AS events,several targeted agents have been developed to fight against pathogens.Here,we summarized recent findings in the field of infection-related splicing,including splicing mechanisms of pathogens and hosts,splicing regulation and aberrant AS events,as well as emerging targeted drugs.We aimed to systemically decode host–pathogen interactions from a perspective of splicing.We further discussed the current strategies of drug development,detection methods,analysis algorithms,and database construction,facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.

关 键 词：Alternative splicing Infectious diseases SPLICEOSOME Regulation mechanism Targeted drug 

分 类 号：R51[医药卫生—内科学]