SARS-CoV-2 has the advantage of competing the iMet–tRNAs with human hosts to allow efficient translation
MOLECULAR GENETICS AND GENOMICS(2020)
Abstract
To better understand the interaction between SARS-CoV-2 and human host and find potential ways to block the pandemic, one of the unresolved questions is that how the virus economically utilizes the resources of the hosts. Particularly, the tRNA pool has been adapted to the host genes. If the virus intends to translate its own RNA, then it has to compete with the abundant host mRNAs for the tRNA molecules. Translation initiation is the rate-limiting step during protein synthesis. The tRNAs carrying the initiation Methionine (iMet) recognize the start codon termed initiation ATG (iATG). Other normal Met-carrying tRNAs recognize the internal ATGs. The tAI of virus genes is significantly lower than the tAI of human genes. This disadvantage in translation elongation of viral RNAs must be compensated by more efficient initiation rates. In the human genome, the abundance of iMet–tRNAs to Met–tRNAs is five times higher than the iATG to ATG ratio. However, when SARS-CoV-2 infects human cells, the iMet has an 8.5-time enrichment to iATG. We collected 58 virus species and found that the enrichment of iMet is higher in all viruses compared to human. Our study indicates that the genome sequences of viruses like SARS-CoV-2 have the advantage of competing for the iMet–tRNAs with host mRNAs. The capture of iMet–tRNAs allows the fast translation initiation and the reproduction of virus itself, which compensates the lower tAI of viral genes. This might explain why the virus could rapidly translate its own RNA and reproduce itself from the sea of host mRNAs. Meanwhile, our study reminds the researchers not to ignore the mutations related to ATGs.
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Key words
SARS-CoV-2,tRNA,Methionine (met),Translation initiation
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