Elevated A-to-I RNA editing in COVID-19 infected individuals

Author:

Merdler-Rabinowicz Rona123ORCID,Gorelik David13,Park Jiwoon45,Meydan Cem4,Foox Jonathan4,Karmon Miriam13,Roth Hillel S13,Cohen-Fultheim Roni13,Shohat-ophir Galit16,Eisenberg Eli7ORCID,Ruppin Eytan2ORCID,Mason Christopher E48910,Levanon Erez Y13ORCID

Affiliation:

1. Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat Gan , Israel

2. Cancer Data Science Lab, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda , MD , USA

3. The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University , Ramat Gan , Israel

4. Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine , New York , NY , USA

5. Laboratory of Virology and Infectious Disease, The Rockefeller University , New York , NY , USA

6. Leslie and Susan Gonda Multidisciplinary Brain Research Center and The Nanotechnology Institute, Bar-Ilan University , Ramat Gan , Israel

7. Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University , Tel Aviv , Israel

8. The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine , New York , NY , USA

9. Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine , New York , NY , USA

10. The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine , New York , NY , USA

Abstract

Abstract Given the current status of coronavirus disease 2019 (COVID-19) as a global pandemic, it is of high priority to gain a deeper understanding of the disease's development and how the virus impacts its host. Adenosine (A)-to-Inosine (I) RNA editing is a post-transcriptional modification, catalyzed by the ADAR family of enzymes, that can be considered part of the inherent cellular defense mechanism as it affects the innate immune response in a complex manner. It was previously reported that various viruses could interact with the host's ADAR enzymes, resulting in epigenetic changes both to the virus and the host. Here, we analyze RNA-seq of nasopharyngeal swab specimens as well as whole-blood samples of COVID-19 infected individuals and show a significant elevation in the global RNA editing activity in COVID-19 compared to healthy controls. We also detect specific coding sites that exhibit higher editing activity. We further show that the increment in editing activity during the disease is temporary and returns to baseline shortly after the symptomatic period. These significant epigenetic changes may contribute to the immune system response and affect adverse outcomes seen in post-viral cases.

Funder

Israel Science Foundation

Igor Tulchinsky

WorldQuant Foundation

Pershing Square Foundation

Ken Griffin and Citadel

GI Research Foundation

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Applied Mathematics,Computer Science Applications,Genetics,Molecular Biology,Structural Biology

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