PhD defence X. (Xumin) Ou

Translational regulation bridges the cellular transcriptome and proteome, and this has become an overarching theme in modern biology and medicine. I herein investigated the role of translational decoding in viral infection and cancer development. In part I, I have established a comprehensive understanding of tRNA biology starting from the genomic identification of tRNA genes to determining the levels of mature tRNAs, and I investigated remodeling of the tRNA landscape in cells infected with HEV, as well as tRNA dysregulation and tRNA based therapeutic potential in the setting of liver cancer. Although the cell has impressive mechanisms to prevent mistranslation from happening, aberrant decoding of codons does occur. I discussed the potential mechanism underlying erroneous translation and established that the main causes are tRNA misdecoding and misacylation. In part II, the implications of translational decoding in viral infection have been demonstrated in both artificially and naturally viral cross-species adaption. We found that the incompatible translation present in a chicken host contributed to the codon usage bias of the duck DHAV insolates and force its artificially viral cross-species adaption from duck to chicken. In coronaviruses including SARS-CoV-2, strong purifying selection is shaped that may contribute to their bat-to-human transmission. The thesis largely enhances our understanding of translation decoding, especially the tRNA-mRNA codon interactions, in virology and cancer biology and holds great promise in developing novel antiviral strategies, anticancer therapy, and new vaccine development via harnessing the tRNA decoding system.

The public defence will take place online at the Prof. Andries Queridoroom, 3rd floor Education Center, Erasmus MC. The ceremony will begin exactly at 13.00 PM.