Author: Siniscalchi, Chiara; Di Palo, Armando; Russo, Aniello; Potenza, Nicoletta
Title: Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation Cord-id: dcwu7gem Document date: 2021_6_7
ID: dcwu7gem
Snippet: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel RNA virus affecting humans, causing a form of acute pulmonary respiratory disorder named COVID-19, declared a pandemic by the World Health Organization. MicroRNAs (miRNA) play an emerging and important role in the interplay between viruses and host cells. Although the impact of host miRNAs on SARS-CoV-2 infection has been predicted, experimental data are still missing. This study started by a bioinformatics prediction of cel
Document: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel RNA virus affecting humans, causing a form of acute pulmonary respiratory disorder named COVID-19, declared a pandemic by the World Health Organization. MicroRNAs (miRNA) play an emerging and important role in the interplay between viruses and host cells. Although the impact of host miRNAs on SARS-CoV-2 infection has been predicted, experimental data are still missing. This study started by a bioinformatics prediction of cellular miRNAs potentially targeting viral RNAs; then, a number of criteria also based on experimental evidence and virus biology were applied, giving rise to eight promising binding miRNAs. Their interaction with viral sequences was experimentally validated by transfecting luciferase-based reporter plasmids carrying viral target sequences or their inverted sequences into the lung A549 cell line. Transfection of the reporter plasmids resulted in a reduction of luciferase activity for five out of the eight potential binding sites, suggesting responsiveness to endogenously expressed miRNAs. Co-transfection of the reporter plasmids along with miRNA mimics led to a further and strong reduction of luciferase activity, validating the interaction between miR-219a-2-3p, miR-30c-5p, miR-378d, miR-29a-3p, miR-15b-5p, and viral sequences. miR-15b was also able to repress plasmid-driven Spike expression. Intriguingly, the viral target sequences are fully conserved in more recent variants such as United Kingdom variant B.1.1.7 and South Africa 501Y.V2. Overall, this study provides a first experimental evidence of the interaction between specific cellular miRNAs and SARS-CoV-2 sequences, thus contributing to understanding the molecular mechanisms underlying virus infection and pathogenesis to envisage innovative therapeutic interventions and diagnostic tools.
Search related documents:
Co phrase search for related documents- accession number and luciferase reporter: 1
- activity reduction and acute sars cov respiratory syndrome coronavirus: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15
- activity reduction and luciferase activity: 1
- activity reduction and luciferase activity reduction: 1
- activity reduction and luciferase reporter: 1
- acute myeloid leukemia and luciferase assay: 1
- acute myeloid leukemia and luciferase reporter: 1, 2
- acute sars cov respiratory syndrome coronavirus and luc luciferase: 1, 2
- acute sars cov respiratory syndrome coronavirus and luciferase activity: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10
- acute sars cov respiratory syndrome coronavirus and luciferase assay: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15
- acute sars cov respiratory syndrome coronavirus and luciferase reporter: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17
- luc luciferase and luciferase activity: 1, 2, 3
- luc luciferase and luciferase assay: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13
- luc luciferase and luciferase reporter: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
- luc luciferase and luciferase reporter construct: 1, 2
Co phrase search for related documents, hyperlinks ordered by date