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Papillomavirus capsid protein expression level depends on the match between codon usage and tRNA availability
1Centre for Immunology & Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.
Journal of Virology
|May 11, 1999
Summary
Papillomavirus (PV) late gene translation is restricted due to codon composition. Modifying these codons or increasing tRNA levels overcomes this restriction, explaining PV gene expression patterns.
Area of Science:
- Molecular Biology
- Virology
- Gene Expression
Background:
- Papillomavirus (PV) mRNA translation is confined to differentiated epithelial cells, despite broader transcription.
- PV late genes exhibit distinct codon composition compared to mammalian genes.
Purpose of the Study:
- To investigate if PV late gene codon composition dictates expression efficiency in specific cell types.
- To determine the role of codon usage versus mRNA structure in PV translation restriction.
Main Methods:
- Constructed synthetic bovine papillomavirus type 1 (BPV1) late genes with modified codon composition.
- Compared expression of wild-type and modified BPV1 late genes in Cos-1 cells.
- Assessed mRNA transcription and protein translation, including in vitro translation assays with added aminoacyl-tRNAs.
Main Results:
- Both wild-type and modified BPV1 genes were transcribed, but only modified genes were translated in Cos-1 cells.
- In vitro translation of wild-type BPV1 mRNA was enhanced by aminoacyl-tRNAs.
- Altering codons in a reporter gene (gfp) to PV usage significantly reduced its translation, not transcription.
Conclusions:
- BPV1 late gene translation is limited by codon composition in Cos-1 cells.
- This limitation can be overcome by codon modification or increased tRNA availability.
- Codon usage, rather than mRNA structure, appears to be the primary factor in PV translation efficiency, potentially explaining tissue-specific expression.