| Autor: |
Eldin P; Institut de Recherche en Infectiologie de Montpellier (IRIM), University of Montpellier, CNRS UMR 9004, 1919 route de Mende, 34293 Montpellier, France., David A; Institut de Génomique Fonctionnelle (IGF), INSERM U1191, 141 Rue de la Cardonille, 34000 Montpellier, France.; Institute for Regenerative Medicine and Biotherapy (IRMB)-Plateforme de Protéomique Clinique (PPC), Institut des Neurosciences de Montpellier (INM), University of Montpellier, CHU Montpellier, INSERM CNRS, 298 Rue du Truel, 34090 Montpellier, France., Hirtz C; Institute for Regenerative Medicine and Biotherapy (IRMB)-Plateforme de Protéomique Clinique (PPC), Institut des Neurosciences de Montpellier (INM), University of Montpellier, CHU Montpellier, INSERM CNRS, 298 Rue du Truel, 34090 Montpellier, France., Battini JL; Institut de Recherche en Infectiologie de Montpellier (IRIM), University of Montpellier, CNRS UMR 9004, 1919 route de Mende, 34293 Montpellier, France., Briant L; Institut de Recherche en Infectiologie de Montpellier (IRIM), University of Montpellier, CNRS UMR 9004, 1919 route de Mende, 34293 Montpellier, France. |
| Abstrakt: |
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 Lys AAA , Gln CAA , Glu GAA , and Arg AGA , which are infrequently used in human genes. In the absence of an adapted tRNA pool, efficient decoding of these codons requires a 5-methoxycarbonylmethyl-2-thiouridine (mcm 5 s 2 ) modification at the U 34 wobble position of the corresponding tRNAs (tLys UUU ; tGln UUG ; tGlu UUC ; tArg UCU ). 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 U 34 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. |
