AsianScientist (May 11, 2020) – A team of researchers led by Professor Narry Kim at the Institute for Basic Science (IBS), South Korea, have published a detailed map of the SARS-CoV-2 transcriptome, paving the way for targeted treatments for COVID-19. Their findings have been published in Cell.
Although the genome of the SARS-CoV-2 virus has been available since January, how the virus transcribes and uses its genome was not known. As an RNA virus, SARS-CoV-2 produces many smaller RNAs called subgenomic RNAs once it enters the host cell. These subgenomic RNAs might be good targets for stopping the progression of COVID-19, the disease called by SARS-CoV-2.
In the present study, Kim and her team have successfully combined two different RNA sequencing methods to dissect the architecture of the SARS-CoV-2 genome. The researchers not only confirmed that the predicted subgenomic RNAs are translated into viral proteins, but also revealed exactly where the genes are located on the genomic RNA.
“Apart from detailing the structure of SARS-CoV-2, we also discovered numerous new RNAs and multiple unknown chemical modification on the viral RNAs. Our work provides a high-resolution map of SARS-CoV-2. This map will help understand how the virus replicates and how it escapes the human defense system,” said Kim, who is the director of the IBS Center for RNA Research.
In addition to confirming that only nine out of the ten previously known subgenomic RNAs exist, the researchers also found that there are dozens of unknown subgenomic RNAs, owing to RNA fusion and deletion events.
“Though it requires further investigation, these molecular events may lead to the relatively rapid evolution of coronavirus. Moreover, we find multiple unknown chemical modifications on the viral RNAs. It is unclear yet what these modifications do, but a possibility is that they may assist the virus to avoid the attack from the host,” explained Kim.
The key to the team’s success in sequencing the transcriptome was pairing two complementary sequencing techniques; DNA nanoball sequencing and nanopore direct RNA sequencing. Conventional RNA sequencing methods usually require a step-by-step process of cutting and converting RNA to DNA before reading RNA. In contrast, nanopore direct RNA sequencing allowed the researchers to directly analyze the entire long viral sequence without fragmentation. DNA nanoball sequencing on the other hand can read only short fragments, but has the advantage of analyzing a large number of sequences with high accuracy.
“We have secured a high resolution gene map of the new coronavirus that guides us where to find each gene on the main SARS-CoV-2 RNAs (transcriptome) as well as all the modified RNAs (epitranscriptome). It is time to explore the functions of the newly discovered genes and the mechanism underlying viral gene fusion. We also have to work on the RNA modifications to see if they play a role in virus replication and immune response. We firmly believe that our study will contribute to the development of diagnostics and therapeutics to combat the virus more effectively,” concluded Kim.
The article can be found at: Kim et al. (2020) The Architecture of SARS-CoV-2 Transcriptome.
Source: Institute for Basic Science; Photo: Shutterstock.
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