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This work was supported by the Agencia Estatal de Investigacion (AEI) (co-supported by FEDER - EU) (Grant PID2022-1393930B-I00 to GG), the CSIC PTI Salud Global (grant SGL2021-03-040 to G.R.) through the NextGenerationEU Fund (regulation 2020/2094) and the Regional Government of Valencia (grant GVA-COVID19/2021/036 to G.R.). J.C.S. and A.G.H.A. are recipients of a pre-doctoral contract from the Generalitat Valenciana (CIACIF-2021-279 and ACIF-2021-202). The central tRNA structure shown in Fig. 4 is adapted from the original figure "The tRNA cloverleaf general" by Yikrazuul under a Creative Commons license (C.C. BY 3.0).

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

Publicat a:Npj Syst Biol Appl. 10 (1): 41- - 2024-04-17 10(1), DOI: 10.1038/s41540-024-00367-z

Autors: Corell-Sierra, Julia; Marquez-Molins, Joan; Marques, Maria-Carmen; Hernandez-Azurdia, Andrea Gabriela; Montagud-Martinez, Roser; Cebria-Mendoza, Maria; Cuevas, Jose M; Albert, Eliseo; Navarro, David; Rodrigo, Guillermo; Gomez, Gustavo

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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.

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