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Updated: Jul 4, 2026
09:14
Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
DMS-informed secondary structure modeling of Epstein-Barr Virus LMP-1 pre-mRNA defines novel elements spanning
Taylor O Eich1, Evelyn C Coppenbarger1, Abdelraouf O Dapour2
1Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa, United States of America.
Plos One
|July 2, 2026
Summary
Researchers mapped RNA structures regulating Epstein-Barr virus (EBV) LMP1 gene splicing using SIRP-seq. These structures, including novel elements near splice sites, may influence EBV-associated cancer development and offer therapeutic targets.
Area of Science:
- Molecular Biology
- Virology
- Structural Biology
Background:
- Epstein-Barr virus (EBV) establishes lifelong latency in most adults and is linked to cancers like Burkitt lymphoma.
- The splicing of the EBV latent membrane protein 1 (LMP1) gene is crucial, but its regulatory RNA structures are unknown.
- Understanding LMP1 RNA structure is key to deciphering EBV pathogenesis and developing targeted therapies.
Purpose of the Study:
- To identify and characterize RNA secondary structures that regulate the splicing of the Epstein-Barr virus LMP1 gene.
- To generate high-resolution structural models of LMP1 pre-mRNA, including alternatively spliced isoforms.
- To investigate the potential role of these RNA structures in EBV-associated malignancies.
Main Methods:
- Application of spliceosome inhibition with RNA probing and sequencing (SIRP-seq) to EBV-infected BJAB-B1 cells.
- Enrichment of pre-mRNA species using the spliceosome inhibitor pladienolide B.
- Integration of chemical probing data with RNA folding algorithms (RNAfold, ScanFold) to predict secondary structures.
Main Results:
- Generation of the first high-resolution secondary structure models for LMP1 pre-mRNA, covering exonic and intronic regions.
- Identification of 11 novel, thermodynamically stable RNA structures within the LMP1 pre-mRNA.
- Discovery of three key structures near the 3' splice site of intron 2, exhibiting alternative conformations potentially affecting splicing.
- Mapping of identified structures to regions with disease-relevant mutations linked to Burkitt lymphoma patient survival.
Conclusions:
- RNA structure plays a significant role in regulating LMP1 splicing.
- Novel RNA structural elements identified near splice junctions provide mechanistic insights into splicing control.
- These structures represent potential therapeutic targets for mitigating EBV-associated diseases, including Burkitt lymphoma.
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