Abstract
The emergence of a new coronavirus (CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for severe respiratory disease in humans termed coronavirus disease of 2019 (COVID-19), became a new global threat for health and the economy. The SARS-CoV-2 genome is about a 29,800-nucleotide-long plus-strand RNA that can form functionally important secondary and higher-order structures called cis-acting RNA elements. These elements can interact with viral proteins, host proteins, or other RNAs and be involved in regulating translation and replication processes of the viral genome and encapsidation of the virus. However, the cis-acting RNA elements and their biological roles in SARS-CoV-2 as well as their comparative analysis in the closely related viral genome have not been well explored, which is very important to understand the molecular mechanism of viral infection and pathogenies. In this study, we used a bioinformatics approach to identify the cis-acting RNA elements in the SARS-CoV-2 genome. Initially, we aligned the full genomic sequence of six different CoVs, and a phylogenetic analysis was performed to understand their evolutionary relationship. Next, we predicted the cis-acting RNA elements in the SARS-CoV-2 genome using the structRNAfinder tool. Then, we annotated the location of these cis-acting RNA elements in different genomic regions of SARS-CoV-2. After that, we analyzed the sequence conservation patterns of each cis-acting RNA element among the six CoVs. Finally, the presence of cis-acting RNA elements across different CoV genomes and their comparative analysis was performed. Our study identified 12 important cis-acting RNA elements in the SARS-CoV-2 genome; among them, Corona_FSE, Corona_pk3, and s2m are highly conserved across most of the studied CoVs, and Thr_leader, MAT2A_D, and MS2 are uniquely present in SARS-CoV-2. These RNA structure elements can be involved in viral translation, replication, and encapsidation and, therefore, can be potential targets for better treatment of COVID-19. It is imperative to further characterize these cis-acting RNA elements experimentally for a better mechanistic understanding of SARS-CoV-2 infection and therapeutic intervention.
Highlights
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes severe respiratory disease in humans, is called the coronavirus disease of 2019 (COVID-19)
We predicted the cis-acting RNA elements in the SARS-CoV-2 genome using the structRNAfinder tool. We modeled these cis-acting RNA elements using a knowledge-based method, RNAComposer, that employs fully automated fragment assembly based on the secondary RNA structure as annotated by the RNAfold algorithm
Our study identified several cis-acting RNA elements in SARS-CoV-2, which could be used to understand how these elements interact with host machinery to regulate viral protein translation, genome replication, packaging, and pathogenesis
Summary
The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes severe respiratory disease in humans, is called the coronavirus disease of 2019 (COVID-19). The single-stranded RNA of the viral genome can form functionally important secondary and higher-order structures called cis-acting RNA elements, such as internal ribosome entry sites, riboswitches, and many others (Liu et al, 2009) These elements can interact with viral proteins, host proteins, or other RNAs and are involved in regulating translation and replication processes of the viral genome as well as encapsidation of the virus (Liu et al, 2009). Our study identified several cis-acting RNA elements in SARS-CoV-2, which could be used to understand how these elements interact with host machinery to regulate viral protein translation, genome replication, packaging, and pathogenesis
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