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Updated: Aug 14, 2026

Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses
Published on: December 29, 2015
Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus
P R Smith1, O de Jesus, D Turner
1Virology and Cell Biology, Imperial College School of Medicine, London W2 1PG, United Kingdom.
Abstract:
CST (BART BARF0) family viral RNAs are expressed in several types of Epstein-Barr virus (EBV) infection, including EBV-associated cancers. Many different spliced forms of these RNAs have been described; here we have clarified the structures of some of the more abundant splicing patterns. We report the first cDNAs representing a full-length CST mRNA from a clone library and further characterize the transcription start. The relative abundance of splicing patterns and genomic analysis of the open reading frames (ORFs) suggest that, in addition to the much studied BARF0 ORF, there may be important products made from some of the upstream ORFs in the CST RNAs. Potential biological functions are identified for two of these. The product of the RPMS1 ORF is shown to be a nuclear protein that can bind to the CBF1 component of Notch signal transduction. RPMS1 can inhibit the transcription activation induced through CBF1 by NotchIC or EBNA-2. The protein product of another CST ORF, A73, is shown to be a cytoplasmic protein which can interact with the cell RACK1 protein. Since RACK1 modulates signaling from protein kinase C and Src tyrosine kinases, the results suggest a possible role for CST products in growth control, perhaps consistent with the abundant transcription of CST RNAs in cancers such as nasopharyngeal carcinoma.
Insights
Epstein-Barr virus (EBV) CST RNAs, found in cancers, have multiple forms. New research identifies novel protein products from these RNAs that may regulate cell growth and signaling pathways.
Area of Science:
- Virology
- Molecular Biology
- Cancer Research
Background:
- CST (BART BARF0) family viral RNAs are expressed during Epstein-Barr virus (EBV) infections, including EBV-associated cancers.
- Previous studies described various spliced forms of these RNAs, but their full structures and functions remain incompletely understood.
Purpose of the Study:
- To clarify the structures of abundant splicing patterns within CST RNAs.
- To identify and characterize novel protein products encoded by CST RNAs and investigate their biological functions.
- To explore the potential roles of these proteins in EBV infection and associated cancers.
Main Methods:
- Cloning and sequencing of full-length CST mRNA cDNAs.
- Genomic analysis of open reading frames (ORFs) within CST RNAs.
- Protein expression and interaction studies, including nuclear/cytoplasmic localization and binding assays.
- Functional assays to assess effects on signal transduction pathways.
Main Results:
- The study reports the first full-length CST mRNA cDNAs and characterizes transcription start sites.
- Genomic analysis revealed potential functional upstream ORFs in addition to the known BARF0 ORF.
- The RPMS1 ORF product is a nuclear protein that binds CBF1, inhibiting Notch signaling.
- The A73 ORF product is a cytoplasmic protein interacting with RACK1, suggesting a role in growth control.
Conclusions:
- CST RNAs encode multiple functional proteins beyond BARF0, including RPMS1 and A73.
- These novel CST protein products have distinct cellular localizations and interact with key signaling molecules (CBF1, RACK1).
- The identified functions suggest CST RNAs and their products play significant roles in EBV pathogenesis and cancer development, particularly in nasopharyngeal carcinoma.
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