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

MERINO, G.; RAAD, J.; BUGNON, L.; YONES, C.; KAMENETZKY, L.; CLAUS, J.; ARIEL, F.; MILSTEIN D.; STEGMAYER, G.

BIOINFORMATICS (OXFORD, ENGLAND)

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2020

1367-4803

Motivation: The Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) hasrecently emerged as the responsible for the pandemic outbreak of thecoronavirus disease (COVID-19). This virus is closely related to coronavirusesinfecting bats and Malayan pangolins, species suspected to be an intermediatehost in the passage to humans. Several genomic mutations affecting viralproteins have been identified, contributing to the understanding of the recentanimal-to-human transmission. However, the capacity of SARS-CoV-2 to encodefunctional putative microRNAs (miRNAs) remains largely unexplored. Results: We have used deep learning to discover 12 candidate stem-loopstructures hidden in the viral protein-coding genome. Among the precursors, theexpression of eight mature miRNAs-like sequences was confirmed in small RNA-seqdata from SARS-CoV-2 infected human cells. Predicted miRNAs are likely totarget a subset of human genes of which 109 are transcriptionally deregulatedupon infection. Remarkably, 28 of those genes potentially targeted bySARS-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 andSARS-CoV-2. The comparison of SARS-CoV-2 pre-miRNA sequences with those frombat and pangolin coronaviruses suggests that single nucleotide mutations couldhave helped its progenitors jumping inter-species boundaries, allowing the gainof novel mature miRNAs targeting human mRNAs. Our results suggest that therecent acquisition of novel miRNAs-like sequences in the SARS-CoV-2 genome mayhave contributed to modulate the transcriptional reprogramming of the new hostupon infection.