부산대학교 도서관

Translational regulation in tissue environments during in vivo viral pathogenesis has rarely been studied due to the lack of translatomes from virus-infected tissues, although a series of translatome studies using in vitro cultured cells with viral infection have been reported. In this study, we exploited tissue-optimized ribosome profiling (Ribo-seq) and severe-COVID-19 model mice to establish the first temporal translation profiles of virus and host genes in the lungs during SARS-CoV-2 pathogenesis. Our datasets revealed not only previously unknown targets of translation regulation in infected tissues but also hitherto unreported molecular signatures that contribute to tissue pathology after SARS-CoV-2 infection. Specifically, we observed gradual increases in pseudoribosomal ribonucleoprotein (RNP) interactions that partially overlapped the trails of ribosomes, being likely involved in impeding translation elongation. Contemporaneously developed ribosome heterogeneity with predominantly dysregulated 5 S rRNP association supported the malfunction of elongating ribosomes. Analyses of canonical Ribo-seq reads (ribosome footprints) highlighted two obstructive characteristics to host gene expression: ribosome stalling on codons within transmembrane domain-coding regions and compromised translation of immunity- and metabolism-related genes with upregulated transcription. Our findings collectively demonstrate that the abrogation of translation integrity may be one of the most critical factors contributing to pathogenesis after SARS-CoV-2 infection of tissues.
SARS-CoV-2 infection: disruption of translation integrity: This study reveals that SARS-CoV-2 exhibits distinct profiles of viral gene expression in tissue microenvironments, with lower levels of subgenomic RNAs and subdued expansion compared to cell lines. Researchers discovered pseudoribosomal ribonucleoprotein (RNP) interactions developing in the lungs during SARS-CoV-2 pathogenesis, which may contribute to the accumulation of small Ribo-seq reads and affect translation elongation. Ribosome heterogeneity with compromised 5 S rRNP association was also observed, suggesting a potential strategy for coping with SARS-CoV-2 pathogenesis by resolving RBP complexes. The findings provide valuable insights into the molecular mechanisms underlying SARS-CoV-2 infection and potential therapeutic targets for COVID-19 treatment.