C/D box snoRNAs in viral infections: RNA viruses use old dogs for new tricks

Abstract

C/D box snoRNAs (SNORDs) are a highly expressed class of non-coding RNAs. Besides their well-established role in rRNA modification, C/D box snoRNAs form protein complexes devoid of fibrillarin and regulate pre-mRNA splicing and polyadenylation of numerous genes. There is an emerging body of evidence for functional interactions between RNA viruses and C/D box snoRNAs. The infectivity of some RNA viruses depends on enzymatically active fibrillarin, and many RNA viral proteins associate with nucleolin or nucleophosmin, suggesting that viruses benefit from their cytosolic accumulation. These interactions are likely reflected by morphological changes in the nucleolus, often leading to relocalization of nucleolar proteins and ncRNAs to the cytosol that are a characteristic feature of viral infections. Knock-down studies have also shown that RNA viruses need specific C/D box snoRNAs for optimal replication, suggesting that RNA viruses benefit from gene expression programs regulated by SNORDs, or that viruses have evolved “new” uses for these humble ncRNAs to advance their prospects during infection.

SnoRNAs and miRNAs Networks Underlying COVID-19 Disease Severity

“…These findings are in line with the relative lymphopenia reported in severe COVID-19 [1]. Captivatingly, siRNA studies targeting candidate snoRNAs provide an evidence of their functional roles in virus-host interactions against numerous viruses, while knock-down studies have demonstrated that RNA viruses require specific C/D box snoRNAs for optimal replication [17]. Thus, a validated COVID-19 miRNA and snoRNAs signature could be a useful tool to discriminate COVID-19 infections from other respiratory viral infections, identify asymptomatic infections, and develop proteins and metabolite-based tests.…”

“…Hence, identification of miRNAs as well as characterization of miRNA-mRNA interactions in SARS-CoV-2 infection is important to understand their role in disease pathogenesis, progression, and severity [13][14][15]. Accumulating evidence is also implicating snoRNAs in numerous physiological and pathological processes, including their interactions with some RNA viruses [16,17]. SnoRNAs have been shown to play a role in ribosomal RNAs (rRNAs) modification and maturation.…”

Blood snoRNAs and miRNAs as predictors of COVID-19 Severity

“…These ndings are in line with the relative lymphopenia reported in severe COVID-19 (1). Captivatingly, siRNA studies targeting candidate snoRNAs provide an evidence of their functional roles in virus-host interactions against numerous viruses ,while knock-down studies have demonstrated that RNA viruses require speci c C/D box snoRNAs for optimal replication (17). Thus, a validated COVID-19 miRNA and snoRNAs signature could be a useful tool to discriminate COVID-19 infections from other respiratory viral infections, identify asymptomatic infections, and develop proteins and metabolite-based tests.…”

Emerging Data on the Diversity of Molecular Mechanisms Involving C/D snoRNAs

“…If most viruses do not encode their own snoRNAs, C/D snoRNAs are recurrently deregulated upon viral infection, e.g., by the Chikungunya virus (CHIKV) [184], by the Murine Cytomegalovirus (MCMV) [185], or the porcine reproductive and respiratory syndrome virus (PRRSV) [186]. Moreover, gene-trap insertional mutagenesis testing 12 distinct viruses has also revealed that, among other host genes, several human snoRNA genes participate in viral replication [187] (for an extensive review of the functional interactions between viruses and C/D snoRNAs, see [188]). Apart from pathological conditions, it appears that the expression of snoRNAs could be uncoupled from the level of ribosome synthesis.…”