Preprint Hypothesis Version 1 This version is not peer-reviewed

SARS-CoV-2 Displays a Suboptimal Codon Usage Bias for Efficient Translation in Human Cells Diverted by Hijacking the tRNA Epitranscriptome

Version 1 : Received: 26 September 2024 / Approved: 26 September 2024 / Online: 27 September 2024 (03:21:40 CEST)

How to cite: ELDIN, P.; DAVID, A.; HIRTZ, C.; BATTINI, J.-L.; BRIANT, L. SARS-CoV-2 Displays a Suboptimal Codon Usage Bias for Efficient Translation in Human Cells Diverted by Hijacking the tRNA Epitranscriptome. Preprints 2024, 2024092124. https://doi.org/10.20944/preprints202409.2124.v1 ELDIN, P.; DAVID, A.; HIRTZ, C.; BATTINI, J.-L.; BRIANT, L. SARS-CoV-2 Displays a Suboptimal Codon Usage Bias for Efficient Translation in Human Cells Diverted by Hijacking the tRNA Epitranscriptome. Preprints 2024, 2024092124. https://doi.org/10.20944/preprints202409.2124.v1

Abstract

Codon bias analysis of SARS-CoV-2 reveals suboptimal adaptation for translation in human cells it infects. The detailed examination of the codons preferentially used by SARS-CoV-2 shows a strong preference for LysAAA, GlnCAA, GluGAA, and Arg AGA infrequently used in human genes. In the absence of an adapted tRNA pool, efficient decoding of these codons requires a 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2) modification at the U34 wobble position of the corresponding tRNAs (tLysUUU; tGlnUUG; tGluUUC; tArgUCU). The optimal translation of SARS-CoV-2 open reading frames (ORFs) may therefore require several adjustments to the host's translation machinery, enabling the highly biased viral genome to achieve a more favorable "Ready-to-Translate" state in human cells. Experimental approaches based on LC-MS/MS quantification of tRNA modifications and on alteration of enzymatic tRNA modification pathways provide strong evidence to support the hypothesis that SARS-CoV-2 induces U34 tRNA modifications and relies on these modifications for its lifecycle. The conclusions emphasize the need for future studies on the evolution of SARS-CoV-2 codon bias and its ability to alter the host tRNA pool through the manipulation of RNA modifications.

Keywords

SARS-CoV-2; codon usage; tRNA; epitranscriptome; translation

Subject

Biology and Life Sciences, Virology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.