C/D‐box snoRNAs form methylating and non‐methylating ribonucleoprotein complexes: Old dogs show new tricks

Abstract

C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non-coding RNAs that have been long known to perform 2′-O-methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader-Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre-mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD can form both methylating and non-methylating ribonucleoprotein complexes, providing an indication of the likely physical basis for such diverse new functions. Thus, SNORDs are more structurally and functionally diverse than previously thought, and their role in gene expression is under-appreciated. The action of SNORDs in non-methylating complexes can be substituted with oligonucleotides, allowing devising therapies for diseases like Prader-Willi syndrome.

A guide to naming human non‐coding RNA genes

“…Some snoRNAs show no sequence complementarity to either rRNAs or snRNAs, suggesting they have an alternative function to the canonical snoRNAs described above. For example, there have been recent reports of snoRNAs involved in diverse functions such as activation of enzymes, or regulation of alternative splicing and mRNA levels (Falaleeva et al, 2017). When snoRNAs were first discovered, they were initially not distinguished from other snRNAs and were therefore assigned "U" numbers, e.g.…”

Small nucleolar RNAs: continuing identification of novel members and increasing diversity of their molecular mechanisms of action

“…One of the first examples of this type of molecular mechanism was the box C/D snoRNA SNORD115 and its implication in the alternative splicing of the serotonin receptor 2C gene (HTR2C) [54]. This regulatory mechanism has been extensively described elsewhere (as reviewed for example in [7,55]), but briefly, the orphan SNORD115 was shown to bind the alternative exon Vb of the HTR2C mRNA, the inclusion of which is necessary for functional activity of the resulting receptor. The binding of SNORD115 to the mRNA was shown to serve two main purposes: prevent exonic splicing silencer elements near this region from being bound by splicing regulator proteins and inhibit the A to I base editing of the mRNA [54,[56][57][58].…”

tRNA fragments (tRFs) populations analysis in mutants affecting tRNAs processing and tRNA methylation

“…The increase of small RNAs derived from snoRNAs observed in Rpp30 mutants (Fig.3A) invited us to study this population in more detail. In Drosophila, snoRNAs >120nt are box H/ACA and play a role in Pseudouridylation whereas snoRNAs <120nt are box C/D snoRNA and play a role in 2'-O-methylation (Huang et al, 2005;Angrisani et al, 2015;Falaleeva et al, 2017). Since RNase P has been shown to participate in snoRNAs maturation in some species (Coughlin et al, 2008) and since snoRNAs molecules can be cleaved to form snoRNA fragments (snoRFs) by enzymes that remains to be elucidated (Falaleeva and Stamm, 2013;Światowy and Jagodzińśki, 2018), we studied a potential role of RNase P in snoRFs biogenesis (Sup.…”