IBS Researchers Completed High-Resolution Genetic Map of SARS-CoV-2

Published : Monday, April 13, 2020, 5:24 pm
ACROFAN=Seunghee Shin | | SNS
 The research team of the Institute for Basic Science (IBS) has completed a high-resolution genetic map of SARS coronavirus 2 (SARS-CoV-2), which is the cause of COVID-19 infections in cooperation with the Korea Center for Disease Control. Professor Kim Bit-naeri, a head of RNA Research Division, and Professor Jang Hye-shik of the Life Science Department of the SNU led the research team.

The team analyzed all RNA transcripts that produce SARS coronavirus 2 in host cells by using two types of next-generation sequencing methods; nanopore direct RNA sequencing and DNA nanoball sequencing. In this analysis, not only the exact location of the virus gene was found, but also RNAs that had not been identified by conventional methods were found, and at least 41 sites of the chemical modifications of the virus RNA occurred.

This made it possible to understand how a virus transcriptome is constructed and to pinpoint where the virus genes are located in the genome. That is, a map to solve the complex and hidden secrets of the SARS coronavirus 2 has been found. Moreover, by producing big data for genomes and transcriptomes, it became possible to provide various information for further research.

▲ The life cycle of SARS coronavirus 2 (Image from IBS)

This is how it works. SARS coronavirus 2 contains an RNA-type gene, not DNA. Viruses penetrate host cells and replicate genomic RNA containing genetic information, and at the same time, transcribe various subgenomic RNA based on the genomic RNA. These subgenomes synthesize several proteins such as spikes, envelopes, etc. that make up the particle structure of the virus and form a completed virus in the host cell with the cloned genes. The virus then escapes the cell and infect the new cells.

In previous studies, genomic information of SARS coronavirus 2 was reported, but it remained at the level of predicting the location of the gene based on genomic RNA information. In this study, the research team experimentally identified subgenome RNAs produced from genomic RNAs and analyzed the genetic information of each transcriptome to find exactly where genes are located on genomic RNAs.

Previously, it was known that there were 10 subgenomic RNAs, but this experiment confirmed that only 9 subgenomic RNAs actually exist. The team has found dozens of more species of RNA produced within the cell. Besides, it was identified that various types of recombinations of subgenomic RNA such as fusion and deletion also frequently occur.

What's more, the team found chemical modifications such as methylation in virus RNA. Various biochemical changes occurring in RNA after transcription are called "epitranscriptomes," as several biochemical changes at the DNA level are called "epigenomes." RNAs that have been modified after transcription may have new and unknown properties, so this modification will help to understand the life cycle and pathogenicity of SARS coronavirus 2.

▲ Genomic RNA and subgenomic RNA composition of SARS coronavirus 2, schematic diagram of viral particle structure (Image from IBS)

The study is expected to contribute to understanding the proliferation principle of the virus, improving diagnostic polymerase chain reaction (PCR), and developing new treatment strategies by providing rich information and detailed maps of the SARS coronavirus 2.

The findings of the study were published in the online edition of Cell, on April 9th.

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