Mahoko Takahashi Ueda, Jun Inamo, Fuyuki Miya, Mihoko Shimada, Kensuke Yamaguchi, Yuta Kochi
{"title":"转录本异构体的功能和动态分析揭示了替代剪接在干扰素反应中的重要作用。","authors":"Mahoko Takahashi Ueda, Jun Inamo, Fuyuki Miya, Mihoko Shimada, Kensuke Yamaguchi, Yuta Kochi","doi":"10.1016/j.xgen.2024.100654","DOIUrl":null,"url":null,"abstract":"<p><p>Type I interferon (IFN-I) plays an important role in the innate immune response through inducing IFN-I-stimulated genes (ISGs). However, how alternative splicing (AS) events, especially over time, affect their function remains poorly understood. We generated an annotation (113,843 transcripts) for IFN-I-stimulated human B cells called isoISG using high-accuracy long-read sequencing data from PacBio Sequel II/IIe. Transcript isoform profiling using isoISG revealed that isoform switching occurred in the early response to IFN-I so that ISGs would gain functional domains (e.g., C4B) or higher protein production (e.g., IRF3). Conversely, isoforms lacking functional domains increased during the late phase of IFN-I response, mainly due to intron retention events. This suggests that isoform switching both triggers and terminates IFN-I responses at the translation and protein levels. Furthermore, genetic variants influencing the isoform ratio of ISGs were associated with immunological and infectious diseases. AS has essential roles in regulating innate immune response and associated diseases.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Functional and dynamic profiling of transcript isoforms reveals essential roles of alternative splicing in interferon response.\",\"authors\":\"Mahoko Takahashi Ueda, Jun Inamo, Fuyuki Miya, Mihoko Shimada, Kensuke Yamaguchi, Yuta Kochi\",\"doi\":\"10.1016/j.xgen.2024.100654\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Type I interferon (IFN-I) plays an important role in the innate immune response through inducing IFN-I-stimulated genes (ISGs). However, how alternative splicing (AS) events, especially over time, affect their function remains poorly understood. We generated an annotation (113,843 transcripts) for IFN-I-stimulated human B cells called isoISG using high-accuracy long-read sequencing data from PacBio Sequel II/IIe. Transcript isoform profiling using isoISG revealed that isoform switching occurred in the early response to IFN-I so that ISGs would gain functional domains (e.g., C4B) or higher protein production (e.g., IRF3). Conversely, isoforms lacking functional domains increased during the late phase of IFN-I response, mainly due to intron retention events. This suggests that isoform switching both triggers and terminates IFN-I responses at the translation and protein levels. Furthermore, genetic variants influencing the isoform ratio of ISGs were associated with immunological and infectious diseases. AS has essential roles in regulating innate immune response and associated diseases.</p>\",\"PeriodicalId\":72539,\"journal\":{\"name\":\"Cell genomics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2024-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell genomics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xgen.2024.100654\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell genomics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xgen.2024.100654","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Functional and dynamic profiling of transcript isoforms reveals essential roles of alternative splicing in interferon response.
Type I interferon (IFN-I) plays an important role in the innate immune response through inducing IFN-I-stimulated genes (ISGs). However, how alternative splicing (AS) events, especially over time, affect their function remains poorly understood. We generated an annotation (113,843 transcripts) for IFN-I-stimulated human B cells called isoISG using high-accuracy long-read sequencing data from PacBio Sequel II/IIe. Transcript isoform profiling using isoISG revealed that isoform switching occurred in the early response to IFN-I so that ISGs would gain functional domains (e.g., C4B) or higher protein production (e.g., IRF3). Conversely, isoforms lacking functional domains increased during the late phase of IFN-I response, mainly due to intron retention events. This suggests that isoform switching both triggers and terminates IFN-I responses at the translation and protein levels. Furthermore, genetic variants influencing the isoform ratio of ISGs were associated with immunological and infectious diseases. AS has essential roles in regulating innate immune response and associated diseases.