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Identification of RNA instability elements in Borna disease virus
Ulrike Siemetzki1, Mundrigi S Ashok, Thomas Briese
1Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.
Virus Research
|September 2, 2009
Summary
Borna disease virus (BDV) gene expression is controlled by RNA stability, not just transcription. Specific RNA sequences within the viral genome destabilize transcripts, influencing protein levels and viral persistence.
Area of Science:
- Virology
- Molecular Biology
- Genomics
Background:
- Borna disease virus (BDV) exhibits unique gene expression strategies, including overlapping reading frames and RNA splicing.
- Viral protein levels in BDV-infected cells deviate from typical transcriptional gradients seen in similar viruses.
Purpose of the Study:
- To investigate novel regulatory mechanisms controlling Borna disease virus gene expression.
- To identify factors influencing the observed non-uniform viral protein levels.
Main Methods:
- Analysis of the third transcription unit of the BDV negative-sense RNA genome.
- Identification and characterization of RNA-destabilizing domains within viral transcripts.
Main Results:
- Two RNA-destabilizing domains were identified in the third transcription unit (nucleotides 2818-2918 and 4022-4071).
- One destabilizing domain located in intron-2 is removed upon splicing, suggesting a splicing-dependent regulatory mechanism.
- These domains explain the observed M>L>G protein gradient, independent of transcription levels.
Conclusions:
- Borna disease virus utilizes mRNA stability as a key regulatory mechanism for gene expression.
- Intronic RNA-destabilizing elements provide a novel strategy for controlling viral protein abundance.
- This mechanism supports the persistent, non-cytopathic nature of BDV infections and explains its reliance on alternative splicing.
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