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A high-resolution temporal atlas of the SARS-CoV-2 translatome and transcriptome

Doyeon Kim, Sukjun Kim, Joori Park, Hee Ryung Chang, Jeeyoon Chang, Junhak Ahn, Heedo Park, June‐Hee Park, Narae Son, Gihyeon Kang, Jeonghun Kim, Kisoon Kim, Man‐Seong Park, Yoon Ki Kim, Daehyun Baek

2021Nature Communications97 citationsDOIOpen Access PDF

Abstract

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infected >200 million people resulting in >4 million deaths. However, temporal landscape of the SARS-CoV-2 translatome and its impact on the human genome remain unexplored. Here, we report a high-resolution atlas of the translatome and transcriptome of SARS-CoV-2 for various time points after infecting human cells. Intriguingly, substantial amount of SARS-CoV-2 translation initiates at a novel translation initiation site (TIS) located in the leader sequence, termed TIS-L. Since TIS-L is included in all the genomic and subgenomic RNAs, the SARS-CoV-2 translatome may be regulated by a sophisticated interplay between TIS-L and downstream TISs. TIS-L functions as a strong translation enhancer for ORF S, and as translation suppressors for most of the other ORFs. Our global temporal atlas provides compelling insight into unique regulation of the SARS-CoV-2 translatome and helps comprehensively evaluate its impact on the human genome.

Topics & Concepts

Atlas (anatomy)Coronavirus disease 2019 (COVID-19)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Transcriptome2019-20 coronavirus outbreakComputational biologyBiologyComputer scienceVirologyMedicineGene expressionGeneticsAnatomyPathologyGeneInfectious disease (medical specialty)DiseaseOutbreakinterferon and immune responsesSARS-CoV-2 and COVID-19 ResearchRNA and protein synthesis mechanisms