tetano
Editor, Senior Moderator
Cells
. 2021 Feb 4;10(2):319.
doi: 10.3390/cells10020319.
A Transcription Regulatory Sequence in the 5' Untranslated Region of SARS-CoV-2 Is Vital for Virus Replication with an Altered Evolutionary Pattern against Human Inhibitory MicroRNAs
Manijeh Mohammadi-Dehcheshmeh[SUP] 1 2 [/SUP], Sadrollah Molaei Moghbeli[SUP] 3 [/SUP], Samira Rahimirad[SUP] 4 [/SUP], Ibrahim O Alanazi[SUP] 5 [/SUP], Zafer Saad Al Shehri[SUP] 6 [/SUP], Esmaeil Ebrahimie[SUP] 1 2 7 [/SUP]
Affiliations
Abstract
Our knowledge of the evolution and the role of untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, is found at the 5' ends of all encoded SARS-CoV-2 transcripts, highlighting its importance. Here, evolution of leader sequence was compared between human pathogenic and non-pathogenic coronaviruses. Then, profiling of microRNAs that can inactivate the key UTR regions of coronaviruses was carried out. A distinguished pattern of evolution in leader sequence of SARS-CoV-2 was found. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with a stable thermodynamic binding energy. Notably, SARS-CoV-2 had a lower binding stability against microRNAs. hsa-MIR-5004-3p was the only human microRNA able to target the leader sequence of SARS and to a lesser extent, also SARS-CoV-2. However, its binding stability decreased remarkably in SARS-COV-2. We found some plant microRNAs with low and stable binding energy against SARS-COV-2. Meta-analysis documented a significant (p < 0.01) decline in the expression of MIR-5004-3p after SARS-COV-2 infection in trachea, lung biopsy, and bronchial organoids as well as lung-derived Calu-3 and A549 cells. The paucity of the innate human inhibitory microRNAs to bind to leader sequence of SARS-CoV-2 can contribute to its high replication in infected human cells.
Keywords: COVID-19; SARS-CoV-2 replication; biomarker; drug repurposing; microRNA; microRNA vaccine; nanoparticle vaccine; variant discovery.
. 2021 Feb 4;10(2):319.
doi: 10.3390/cells10020319.
A Transcription Regulatory Sequence in the 5' Untranslated Region of SARS-CoV-2 Is Vital for Virus Replication with an Altered Evolutionary Pattern against Human Inhibitory MicroRNAs
Manijeh Mohammadi-Dehcheshmeh[SUP] 1 2 [/SUP], Sadrollah Molaei Moghbeli[SUP] 3 [/SUP], Samira Rahimirad[SUP] 4 [/SUP], Ibrahim O Alanazi[SUP] 5 [/SUP], Zafer Saad Al Shehri[SUP] 6 [/SUP], Esmaeil Ebrahimie[SUP] 1 2 7 [/SUP]
Affiliations
- PMID: 33557205
- DOI: 10.3390/cells10020319
Abstract
Our knowledge of the evolution and the role of untranslated region (UTR) in SARS-CoV-2 pathogenicity is very limited. Leader sequence, originated from UTR, is found at the 5' ends of all encoded SARS-CoV-2 transcripts, highlighting its importance. Here, evolution of leader sequence was compared between human pathogenic and non-pathogenic coronaviruses. Then, profiling of microRNAs that can inactivate the key UTR regions of coronaviruses was carried out. A distinguished pattern of evolution in leader sequence of SARS-CoV-2 was found. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with a stable thermodynamic binding energy. Notably, SARS-CoV-2 had a lower binding stability against microRNAs. hsa-MIR-5004-3p was the only human microRNA able to target the leader sequence of SARS and to a lesser extent, also SARS-CoV-2. However, its binding stability decreased remarkably in SARS-COV-2. We found some plant microRNAs with low and stable binding energy against SARS-COV-2. Meta-analysis documented a significant (p < 0.01) decline in the expression of MIR-5004-3p after SARS-COV-2 infection in trachea, lung biopsy, and bronchial organoids as well as lung-derived Calu-3 and A549 cells. The paucity of the innate human inhibitory microRNAs to bind to leader sequence of SARS-CoV-2 can contribute to its high replication in infected human cells.
Keywords: COVID-19; SARS-CoV-2 replication; biomarker; drug repurposing; microRNA; microRNA vaccine; nanoparticle vaccine; variant discovery.