Zika virus reprograms the host tRNA epitranscriptome to adapt translation to A-ending codon bias Article Swipe
Patrick Eldin
,
Éric Bernard
,
Cathrine Broberg Vågbø
,
Lynn George
,
Masahiko Ajiro
,
Masatoshi Hagiwara
,
Geir Slupphaug
,
Laurence Briant
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.06.03.657606
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.06.03.657606
The codon usage bias of the Zika virus (ZIKV) genome is skewed towards AA-ending codons, which are preferentially decoded by U34-modified cognate tRNAs. This contrasts with the human host’s preference for AG-ending codons, suggesting that ZIKV may exploit specific tRNA modifications to optimize protein synthesis within human cells. To test this hypothesis, we used codon-biased eGFP sensors and found that ZIKV infection transiently increased the expression of AA-biased GFP at the expense of AG-biased GFP. Mass spectrometry analysis further showed that ZIKV virus infection increases mcm 5 s 2 U 34 tRNA modification content in host cells. In ELP1-deficient cells, which exhibit reduced U 34 modifications, ZIKV replication was impaired. Enhancing U 34 modification through using a small molecule known to restore ELP1 expression, rescued viral replication in these cells. Moreover, CRISPR/Cas9 and shRNA-mediated knockdown of key enzymes involved in U 34 modification, ELP1, ALKBH8, and CTU1, significantly reduced ZIKV replication. Collectively, these results provide strong evidence that ZIKV reprograms the host tRNA epitranscriptome and exploits host cell tRNA modifications, particularly at the wobble position U 34 , to optimize translation of its own proteins and promote viral replication.
Related Topics
Concepts
Translation (biology)
Host (biology)
Transfer RNA
Biology
Computer science
Genetics
RNA
Gene
Messenger RNA
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.06.03.657606
- https://www.biorxiv.org/content/biorxiv/early/2025/06/03/2025.06.03.657606.full.pdf
- OA Status
- green
- Cited By
- 2
- References
- 76
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411034889
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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- DOI
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https://doi.org/10.1101/2025.06.03.657606Digital Object Identifier
- Title
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Zika virus reprograms the host tRNA epitranscriptome to adapt translation to A-ending codon biasWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
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2025-06-03Full publication date if available
- Authors
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Patrick Eldin, Éric Bernard, Cathrine Broberg Vågbø, Lynn George, Masahiko Ajiro, Masatoshi Hagiwara, Geir Slupphaug, Laurence BriantList of authors in order
- Landing page
-
https://doi.org/10.1101/2025.06.03.657606Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2025/06/03/2025.06.03.657606.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2025/06/03/2025.06.03.657606.full.pdfDirect OA link when available
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Translation (biology), Host (biology), Transfer RNA, Biology, Computer science, Genetics, RNA, Gene, Messenger RNATop concepts (fields/topics) attached by OpenAlex
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2Total citation count in OpenAlex
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2025: 2Per-year citation counts (last 5 years)
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76Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2952067440, https://openalex.org/W2773417632, https://openalex.org/W2042530028, https://openalex.org/W2912327568, https://openalex.org/W3034099779, https://openalex.org/W3174385640, https://openalex.org/W2899317755, https://openalex.org/W2084241014, https://openalex.org/W2127168227, https://openalex.org/W2281124081, https://openalex.org/W2933062146, https://openalex.org/W2530359606, https://openalex.org/W2605842901, https://openalex.org/W2496762555, https://openalex.org/W2906608530, https://openalex.org/W2942949465, https://openalex.org/W2768663724, https://openalex.org/W2908171763, https://openalex.org/W252557772, https://openalex.org/W2148399893, https://openalex.org/W2006734870, https://openalex.org/W2746450357, https://openalex.org/W1607969426, https://openalex.org/W2801391821, https://openalex.org/W1979117468, https://openalex.org/W2121006987, https://openalex.org/W1974762136, https://openalex.org/W3184199990, https://openalex.org/W2601439197, https://openalex.org/W2739240461, https://openalex.org/W2760793316, https://openalex.org/W2762425132, https://openalex.org/W4400350080, https://openalex.org/W4401808896, https://openalex.org/W3128038046, https://openalex.org/W4361019769, https://openalex.org/W4220681240, https://openalex.org/W4408082111, https://openalex.org/W2808130319, https://openalex.org/W2151621038, https://openalex.org/W4403871314, https://openalex.org/W2117312105, https://openalex.org/W1996339094, https://openalex.org/W2019546125, https://openalex.org/W2095475642, https://openalex.org/W2066251617, https://openalex.org/W3084186667, https://openalex.org/W4399172792, https://openalex.org/W4290805640, https://openalex.org/W4388408171, https://openalex.org/W4400869974, https://openalex.org/W2599638726, https://openalex.org/W2808878318, https://openalex.org/W2507412157, https://openalex.org/W2793644763, https://openalex.org/W2558875419, https://openalex.org/W2922815849, https://openalex.org/W2803056412, https://openalex.org/W2953584706, https://openalex.org/W2997932505, https://openalex.org/W2526388434, https://openalex.org/W2762528019, https://openalex.org/W3048128711, https://openalex.org/W2140870757, https://openalex.org/W2116429329, https://openalex.org/W2170984819, https://openalex.org/W2153562609, https://openalex.org/W2159686118, https://openalex.org/W1617495083, https://openalex.org/W2064295826, https://openalex.org/W4394694796, https://openalex.org/W2144362290, https://openalex.org/W2099540110, https://openalex.org/W2944788703, https://openalex.org/W2163445749, https://openalex.org/W2167380395 |
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| abstract_inverted_index.5 | 87 |
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