Novel SARS-CoV-2 encoded small RNAs in the passage to humans

Abstract

Motivation The Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) has recently emerged as the responsible for the pandemic outbreak of the coronavirus disease (COVID-19). This virus is closely related to coronaviruses infecting bats and Malayan pangolins, species suspected to be an intermediate host in the passage to humans. Several genomic mutations affecting viral proteins have been identified, contributing to the understanding of the recent animal-to-human transmission. However, the capacity of SARS-CoV-2 to encode functional putative microRNAs (miRNAs) remains largely unexplored. Results We have used deep learning to discover 12 candidate stem-loop structures hidden in the viral protein-coding genome. Among the precursors, the expression of eight mature miRNAs-like sequences was confirmed in small RNA-seq data from SARS-CoV-2 infected human cells. Predicted miRNAs are likely to target a subset of human genes of which 109 are transcriptionally deregulated upon infection. Remarkably, 28 of those genes potentially targeted by SARS-CoV-2 miRNAs are down-regulated in infected human cells. Interestingly, most of them have been related to respiratory diseases and viral infection, including several afflictions previously associated with SARS-CoV-1 and SARS-CoV-2. The comparison of SARS-CoV-2 pre-miRNA sequences with those from bat and pangolin coronaviruses suggests that single nucleotide mutations could have helped its progenitors jumping inter-species boundaries, allowing the gain of novel mature miRNAs targeting human mRNAs. Our results suggest that the recent acquisition of novel miRNAs-like sequences in the SARS-CoV-2 genome may have contributed to modulate the transcriptional reprogramming of the new host upon infection.

Multilevel systems biology analysis of lung transcriptomics data identifies key miRNAs and potential miRNA target genes for SARS-CoV-2 infection

“…The hsa-miR-17-5p was identified as another significant miRNA in our research. TNF expression in leukaemia cells is inhibited by hsa-miR-17, which binds to TNF's 3′-UTR [ 63 , 64 ]. During the IV infection, has-miR-17-3p was found in human alveolar basal epithelial cells (HBEpC) [ 64 ].…”

The miRNA: a small but powerful RNA for COVID-19

“…[ 71 ] also discovered the SARS-CoV-2 encoded miRNAs by using deep learning. Target genes of these miRNAs were closely related to respiratory diseases and viral infection, particularly, some of which have been reported to be surely morbigenous genes that induced SARS-CoV-1 and SARS-CoV-2 [ 71 ]. Besides, another study further explored the function of SARS-CoV-2 encoded miRNAs in detail [ 64 ].…”

GUIdEStaR (G-quadruplex, uORF, IRES, Epigenetics, Small RNA, Repeats), the integrated metadatabase in conjunction with neural network methods

“…It is readily applicable to artificial intelligence (AI) methods. [17,18]. We included attribute selection in SARS-CoV-2 infection as a case study to demonstrate the database usage.…”

“…Since January 2020 (formal news publication on Covid 19 by WHO), variants with a large number of mutations have emerged. It is important to understand what functions small RNAs originated from corona-virus play to reprogram host transcription [17, 18]. We included attribute selection in SARS-CoV-2 infection as a case study to demonstrate the database usage.…”

“…Covid 19 pandemic has changed our lives globally. It is important to understand what functions small RNAs that are originated from corona-virus play to reprogram host transcription [21,22]. SARS-CoV-2 encoded vs. human encoded small RNAs may have different requirements or affinities for target interaction.…”