SARS-CoV-2 remodels the landscape of small non-coding RNAs with infection time and symptom severity

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The study explores how SARS-CoV-2 affects small non-coding RNAs in patients with varying symptom severity through RNA sequencing analysis of nasopharyngeal swab samples. The results show significant alterations in various types of sncRNAs, with a decrease in miRNA expression especially in severe cases. Specific tRNA-derived small RNAs were identified as potential biomarkers for viral presence and disease severity prediction. These findings offer insights into host responses to the virus and suggest potential diagnostic and therapeutic strategies.

Abstract

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has significantly impacted global health, stressing the necessity of basic understanding of the host response to this viral infection. In this study, we investigated how SARS-CoV-2 remodels the landscape of small non-coding RNAs (sncRNA) from a large collection of nasopharyngeal swab samples taken at various time points from patients with distinct symptom severity. High-throughput RNA sequencing analysis revealed a global alteration of the sncRNA landscape, with abundance peaks related to species of 21-23 and 32-33 nucleotides. Host-derived sncRNAs, including microRNAs (miRNAs), transfer RNA-derived small RNAs (tsRNAs), and small nucleolar RNA-derived small RNAs (sdRNAs) exhibited significant differential expression in infected patients compared to controls. Importantly, miRNA expression was predominantly down-regulated in response to SARS-CoV-2 infection, especially in patients with severe symptoms. Furthermore, we identified specific tsRNAs derived from Glu- and Gly-tRNAs as major altered elements upon infection, with 5’ tRNA halves being the most abundant species and suggesting their potential as biomarkers for viral presence and disease severity prediction. Additionally, down-regulation of C/D-box sdRNAs and altered expression of tinyRNAs (tyRNAs) were observed in infected patients. These findings provide valuable insights into the host sncRNA response to SARS-CoV-2 infection and may contribute to the development of further diagnostic and therapeutic strategies in the clinic.

Introduction

The outbreak of pneumonia that began at the end of

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