Genetic study reveals similarities and differs

image: Researchers at the University of Tokyo and the University of Tsukuba have identified specific areas of virus genomes that are shared with many other evolutionarily similar viruses. The hairpin shape of these parts of the virus genome can help viruses bypass a host’s immune system. Due to a few important mutations, the genomic area named COV001 does not form a hairpin structure in the SARS virus (top left), but does in the COVID-19 virus (top right).
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Credit: First published in Wakida et al. 2020, DOI: 10.1016 / j.bbrc.2020.05.008

Researchers have identified specific portions of the genetic codes of COVID-19 and SARS viruses that can promote virus life cycles. The new technique is researchers’ first tool to determine which genetic sequences stored as RNA – the chemical cousin of DNA – are more stable.

“The current pandemic is very serious and we want to contribute to the global acceleration of research on coronaviruses. Our research includes many types of viruses, but we have decided to focus on our findings on coronaviruses, ”said Professor Nobuyoshi Akimitsu, research team leader. who carried out the work and an expert on how cells resist stress at the Isotope Science Center at the University of Tokyo.

Many families of viruses – including influenza viruses and coronaviruses – store their genetic sequence as RNA, which sneaks into human cells and prompts them to make more viruses. Viruses need their RNA to remain stable, resisting the efforts of the host’s immune system to break down their RNA.

The research team named their technique Fate-seq because it aims to determine the fate of a genetic sequence, whether it will persist or degrade based on its stability.

“The Fate-seq technique is a very simple idea. We combined existing technologies in a new way,” Akimitsu explained.

To perform Fate-seq, the researchers first cut a genome into short fragments. Even extremely dangerous pathogens become harmless when researchers work only with short, separated, and chopped fragments of their genome.

Researchers synthesized RNAs from fragments of viral genomes and examined their fate, that is, stability, using next-generation sequencing, which allows researchers to quickly and simultaneously identify the exact sequence individual strands of RNA. Computer programs can then identify patterns or interesting differences in the genetic sequences to be studied in more detail.

The researchers studied 11,848 RNA sequences from 26 viral genomes, including that of SARS-CoV, the virus that causes SARS, sudden acute respiratory syndrome that killed 774 people in the first half of 2003. The researchers identified a total of 625 stable RNA fragments. Of the stable RNA fragments, 21 were from SARS-CoV.

The researchers compared the 21 stable genome fragments of SARS-CoV to the complete genetic sequence data available for other types of coronavirus. Two of the stable fragments of SARS-CoV are very common in other similar evolutionary coronaviruses, including the virus that causes COVID-19, SARS-CoV-2.

Predictive models have shown that these two stable RNA fragments probably form rod and loop structures. Stems and loops are short pieces of RNA that, instead of staying in a straight line, bend forward and bind on themselves, forming a hairpin shape.

Specifically, one of the stable fragments only forms a stem and loop in the COVID-19 virus, not the SARS virus due to the few small but important differences in the RNA codes of the viruses.

“The stem and loop structure of this genetic fragment of SARS-CoV-2 is very stable in computer models and we propose that this structure could improve virus survival,” Akimitsu said.

In addition to better understanding dangerous viruses, researchers hope to use Fate-seq to understand the basic rules of RNA stability and to advance new types of drugs. Human cells use RNA as an intermediary messenger between DNA and protein. Designing RNA-based drugs that are stable and easy for cells to translate into proteins could treat genetic diseases without the risk of damaging our DNA.


This research was carried out with collaborators from the University of Tsukuba and is a peer-reviewed publication in the journal Biochemical and biophysical research communications.

research article

Hiroyasu Wakida, Kentaro Kawata, Yuta Yamaji, Emi Hattori, Takaho Tsuchiya, Youichiro Wada, Haruka Ozaki, Nobuyoshi Akimitsu. May 6, 2020. Stability of RNA Sequences Derived from the Coronavirus Genome in Human Cells. Biochemical and biophysical research communications. DOI: 10.1016 / j.bbrc.2020.05.008

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Akimitsu Lab: Isotope Science Center (in Japanese):

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