Abstract

Coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, enters the cell by binding the cell surface proteins: angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The expression of these proteins varies significantly in individual organs and tissues of the human body. One of the proteins’ expression regulation mechanisms is based on the activity of the microRNA (miRNA) molecules, small non-coding RNAs, the most important function of which is the post-transcriptional negative regulation of gene expression. The study was aimed to investigate the mechanisms of the interactions between miRNA isoforms and ACE2/TMPRSS2 genes in the colon tissues known for the high level of expression of the described enzymes. The search for interactions was performed using the correlation analysis applied to the publicly available paired mRNA/miRNA sequencing data of colon tissues. Among the others, such miRNAs as miR-30c and miR-200c were identified known for their involvement in the coronavirus infection and acute respiratory distress syndrome pathogenesis. Thus, new potential mechanisms for the ACE2 and TMPRSS2 enzymes regulation were ascertained, as well as their possible functional activity in a cell infected with coronavirus.

Highlights

  • The rapid and progressive spread of the COVID-19 infection caused by the SARS-CoV-2 coronavirus deeply affected the health of hundreds of thousands of people, which became a serious challenge to healthcare systems and global economic stability

  • The angiotensinconverting enzyme 2 (ACE2) and TMPRSS2 expression at the mRNA level turned out to be very high: TMPRSS2 was in the list of the most highly expressed genes (1%), and the ACE2 expression was between the 93rd and 94th percentiles, which was fully consistent with published data [13]

  • To search for miRNA isoforms interacting with ACE2 and TMPRSS2 enzymes, we performed the integrated analysis of the paired mRNA and miRNA expression in the normal colon tissues’ sample

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Summary

Introduction

Целью работы было выявить механизмы взаимодействия изоформ микроРНК и генов AПФ2 / TMPRSS2 в тканях толстого кишечника, известных высоким уровнем экспрессии указанных ферментов. Ключевые слова: COVID-19, SARS-CoV-2, AПФ2, TMPRSS2, микроРНК, изоформа микроРНК, острый респираторный дистресс-синдром, коронавирус Финансирование: работа выполнена при поддержке гранта Министерства образования и науки Российской Федерации (проект RFMEFI61618X0092). It is assumed that the greater virulence of SARS-CoV-2 compared to other coronaviruses can be explained by the S1 protein’s significantly higher affinity for ACE2. This mechanism of the SARS-CoV-2 entering the cell leads to the loss of ACE2 on the cell surface, thereby contributing to chronic lung function impairment and severe tissue fibrosis [2]. This is because the most important role in binding to the target mRNA is played by the miRNA region between the 5' nucleotides 2–7 (seed region) [6]

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