Virus-induced codon-specific reprogramming to favor viral RNA translation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA600267 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10859254_1.fastq.gz | Fastqsanger.gz | |||
| SRR10859254_2.fastq.gz | Fastqsanger.gz | |||
| SRR10859255_1.fastq.gz | Fastqsanger.gz | |||
| SRR10859255_2.fastq.gz | Fastqsanger.gz | |||
| SRR10859256_1.fastq.gz | Fastqsanger.gz |
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Project description:How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in suboptimal codons remains a puzzling question. By integrating subcellular fractionation and transcriptome-wide analyses of translation in CHIKV-infected human cells, we demonstrate an unanticipated virus-induced reprogramming of the host translation machinery to favor translation of viral RNA over cellular genes featuring optimal codon usage. This reprogramming was specifically apparent at the endoplasmic reticulum (ER), the preferred translation compartment of CHIKV RNA, and it is mediated by the wobble uridine 34 tRNA modification enzyme KIAA1456 whose expression is enhanced upon viral infection. Since KIAA1456 itself is encoded by a CHIKV-like codon usage, infection triggers a positive feed-back loop that ensures efficient virus protein production. Our findings demonstrate an unprecedented interplay of viruses with the host tRNA epitranscriptome to favor viral protein expression.
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Project description:The precise interplay between the mRNA codon and the tRNA anticodon is crucial for ensuring efficient and accurate translation by the ribosome. The insertion of RNA nucleobase derivatives in the mRNA allowed us to modulate the stability of the codon-anticodon interaction in the decoding site of bacterial and eukaryotic ribosomes, allowing an in-depth analysis of codon recognition. In addition to a quantitative analysis of the protein products that are formed in dependence of the modified codons, the interpretation of these RNA nucleobase derivatives by the ribosomal decoding site was also determined. For each modification, the translated peptides from the bacterial and eukaryotic systems were purified and analyzed by mass spectrometry.
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