Jerome M. Edwards , Ambar Kachale , Spencer R. McCleery , Gabrielle A. Law , Vivek Patel , Victoria M. D’Souza , Vincent V. Pham
{"title":"埃博拉病毒转录调控信号在两种结构构象之间平衡以影响VP30的结合。","authors":"Jerome M. Edwards , Ambar Kachale , Spencer R. McCleery , Gabrielle A. Law , Vivek Patel , Victoria M. D’Souza , Vincent V. Pham","doi":"10.1016/j.jmb.2025.169464","DOIUrl":null,"url":null,"abstract":"<div><div>The transcription of ebolavirus (EBOV) genomes is a major checkpoint in the viral life cycle. Altering the transcription regulatory signal (TRS), an RNA hairpin that forms in the 3′ leader sequence of EBOV, affects transcription in a VP30-dependent manner. How this mechanistically occurs is currently unknown. Here, we find that the TRS primarily equilibrates between two structures that differ in their loops. Mutational studies demonstrate that the entire hairpin structure is important in directing both VP30 binding and regulating EBOV transcriptional activity, with the loop being the principal structural element. In doing so, we highlight that the TRS structure is a critical determinant of EBOV transcription.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 24","pages":"Article 169464"},"PeriodicalIF":4.5000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Ebolavirus Transcription Regulatory Signal Equilibrates Between Two Structural Conformations to Affect VP30 Binding\",\"authors\":\"Jerome M. Edwards , Ambar Kachale , Spencer R. McCleery , Gabrielle A. Law , Vivek Patel , Victoria M. D’Souza , Vincent V. Pham\",\"doi\":\"10.1016/j.jmb.2025.169464\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The transcription of ebolavirus (EBOV) genomes is a major checkpoint in the viral life cycle. Altering the transcription regulatory signal (TRS), an RNA hairpin that forms in the 3′ leader sequence of EBOV, affects transcription in a VP30-dependent manner. How this mechanistically occurs is currently unknown. Here, we find that the TRS primarily equilibrates between two structures that differ in their loops. Mutational studies demonstrate that the entire hairpin structure is important in directing both VP30 binding and regulating EBOV transcriptional activity, with the loop being the principal structural element. In doing so, we highlight that the TRS structure is a critical determinant of EBOV transcription.</div></div>\",\"PeriodicalId\":369,\"journal\":{\"name\":\"Journal of Molecular Biology\",\"volume\":\"437 24\",\"pages\":\"Article 169464\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022283625005303\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022283625005303","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The Ebolavirus Transcription Regulatory Signal Equilibrates Between Two Structural Conformations to Affect VP30 Binding
The transcription of ebolavirus (EBOV) genomes is a major checkpoint in the viral life cycle. Altering the transcription regulatory signal (TRS), an RNA hairpin that forms in the 3′ leader sequence of EBOV, affects transcription in a VP30-dependent manner. How this mechanistically occurs is currently unknown. Here, we find that the TRS primarily equilibrates between two structures that differ in their loops. Mutational studies demonstrate that the entire hairpin structure is important in directing both VP30 binding and regulating EBOV transcriptional activity, with the loop being the principal structural element. In doing so, we highlight that the TRS structure is a critical determinant of EBOV transcription.
期刊介绍:
Journal of Molecular Biology (JMB) provides high quality, comprehensive and broad coverage in all areas of molecular biology. The journal publishes original scientific research papers that provide mechanistic and functional insights and report a significant advance to the field. The journal encourages the submission of multidisciplinary studies that use complementary experimental and computational approaches to address challenging biological questions.
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