Circular RNAs Detected in SARS-Cov-2: A Potential Robust Biomarker for COVID19

Xiaoqi Li
Department of Neurology
Division of Basic Neuroscience
Poster Overview

The COVID-19 pandemic has severely impacted public health and economies worldwide. In the United States alone, more than 5 million people have tested positive, typically based on tests that detect the presence of viral RNA. Most RNA molecules (including those made by viruses) are linear chains, but recently it has been found that cells can also make circular RNAs, which are much more stable than their linear counterparts. To explore the possibility that SARS-Cov-2 virus can give rise to circular RNAs, we re-examined the published data from a recent study of viral RNAs. We discovered evidence for 39 possible circRNAs derived from the SARS-Cov-2 genome. If their existence is confirmed, these novel RNAs may represent a useful biomarker for COVID-19 infection.

Scientific Abstract

The SARS-Cov-2 virus responsible for COVID19 has been detected in city sewage in the Netherlands. To track and slow down the spread of COVID-19, detecting the virus RNA effectively is the key. However, most detection methods target linear mRNAs (or their corresponding cDNAs), which is limited by their susceptibility to degradation and short half-life. Circular RNAs (circRNA) represent a novel class of RNAs that arise from back-splicing of transcripts, forming a stable circular structure. The average half-life of circRNAs can be up to 48 hours, 10 times longer than normal linear mRNAs. A recent study (Kim et al. 2020) has provided a preliminary snapshot of the SARS-Cov-2 transcriptome, but not mentioned the possible existence of virally derived circRNAs. We have re-analyzed their RNAseq data using two novel computational methods in an attempt to identify circRNAs. We find evidence for 39 candidate circRNAs, the most abundant of which is supported by 680 back-spliced reads. Thirty of these candidate circRNAs are transcribed from non-exon regions, suggesting a more complex picture of SARS-Cov-2 transcriptome. While further experimental validation is needed, our analysis suggests that circRNAs could be a stable and robust biomarker for SARS-Cov-2 infection in environmental samples and biospecimens.

Clinical Implications
Our analysis suggests that SARS-Cov-2 can produce novel circular forms of RNA. If their presence is confirmed by qPCR, these circular RNAs could lead to new tests for COVID-19 infection, both in individual patient samples and in community sewage.
Research Areas
Authors
Xiaoqi Li, Xianjun Dong
Principal Investigator
Xianjun Dong

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