A Prion‐Like Domain in EBV EBNA1 Promotes Phase Separation and Enables SRRM1 Splicing
Source abstract
Abstract
Abstract Epstein‐Barr virus (EBV) nuclear antigen 1 (EBNA1) is necessary to maintain stability of EBV episomes, EBV replication, and causes host genomic instability and promotes tumor cells survival. Recent studies have shown that viruses utilize liquid–liquid phase separation (LLPS) within host cells to form sub‐cellular compartments known as “virus factories”. Prion‐like domains (PrLDs), which resemble structural domains of low complexity, are shown to drive LLPS in vivo. In the current study, a PrLD is identified in EBNA1 and aggregation of EBNA1 proteins is observed in EBV‐positive tumors. EBNA1 condensate interacting molecules are examined and are found that EBNA1 interacts with the splicing factor SRSF1 to regulate alternative splicing of SRRM1 and promote tumor progression. Deleting the EBNA1 PrLD results in defects in protein aggregation, LLPS, alternative splicing regulation, and nasopharyngeal carcinoma cells proliferation. Targeting the PrLD of EBNA1 inhibits the formation of protein aggregation, promotes alternative splicing of SRRM1, and inhibits the progression of nasopharyngeal carcinoma. Here, we report for the first time that EBNA1, a protein from the human oncogenic virus EBV, is a prion‐like protein, combining algorithm prediction and experimental validation. That implies a possible molecular pathogenic mechanism of EBNA1 in neurodegenerative diseases.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: RNA Research and Splicing · RNA modifications and cancer · RNA regulation and disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan 410013 China
Cancer Research Institute Xiangya School of Basic Medical Science Central South University Changsha Hunan 410078 China
NHC Key Laboratory of Carcinogenesis Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Hunan Key Laboratory of Nonresolving Inflammation and Cancer Hunan Key Laboratory of Translational Radiation Oncology Changsha Hunan 410078 China
Department of Pathology The First Affiliated Hospital of Guilin Medical University Guilin Guangxi 541001 China
Department of Immunology Changzhi Medical College Changzhi Shanxi 046000 China
Department of Pathology Xiangya Hospital Central South University Changsha Hunan 410008 China
Department of Pathology the Second Xiangya Hospital Central South University Changsha Hunan 410011 China
Department of Clinical Laboratory Xiangya Hospital Central South University Changsha 410008 China
College of Life Sciences Northwest A&F University Yangling Shaanxi 712100 China
Funding
Postdoctoral Science Foundation of Central South University · China Postdoctoral Science Foundation · Science and Technology Program of Hunan Province · National Natural Science Foundation of China
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