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

Abstract

Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we present these pieces of evidence in light of the current comprehension of the molecular mechanisms that control C/D snoRNA expression and function. From this inventory emerges that an accurate description of these activities at a molecular level is required to let the snoRNA field enter in a second age of maturity.

Phylogenetic and Molecular Analyses Identify SNORD116 Targets Involved in the Prader–Willi Syndrome

“…It will be important to identify direct RNA–RNA interactions in tissues that are relevant for SNORD116 physiopathology, as well as to confirm a functional effect at the organismal level, for example, in mouse models. To go further, we invite readers to consult recent reviews that provide an extended discussion on the identification of snoRNA functions ( Bergeron et al 2020 ; Bratkovič et al 2020 ; Baldini et al 2021 ). These approaches could represent a long but necessary effort.…”

Systematic Identification and Functional Validation of New snoRNAs in Human Muscle Progenitors

“…To capture the snoRNAome in a given cellular context, other strategies have been designed. The TGIRT-seq is a structure-based approach dedicated to the identification of snoRNAs, with a slight bias towards highly structured SNORAs, whereas the PAR-CLIP is dedicated to the identification of ncRNAs co-precipitated with a core proteins of a given RNP [ 34 , 35 ], suggesting that they are indeed functional snoRNAs, with the limitation that certain snoRNAs belong to non-canonical snoRNPs (reviewed in [ 48 ]). Another major limitation of such bioinformatics or sequencing approaches is that they can also lead to false identification of non-functional genes or pseudogenes products that resemble snoRNAs [ 49 ].…”

“…We then confirmed the incorporation of almost all snoRNA candidates into snoRNP complexes corroborating the functionality of the new snoRNAs. Of note, we only assessed interactions between snoRNAs and the snoRNP enzymes Dyskerin and Fibrillarin, although some snoRNAs interact with non-conventional protein partners to fulfill non-traditional functions [ 48 , 54 ]. For example, SNORD13 does not associate with Fibrillarin but can guide RNA acetylation by the RNA acetyltransferase NAT10 on the 18S rRNA ([ 55 , 56 , 57 ], reviewed in [ 58 ]).…”

A contemporary review of snoRNAs in cardiovascular health: RNA modification and beyond

“… 21 SNORDs form complexes with four specific proteins—fibrillarin, nucleolar protein 56, nucleolar protein 58, and small nuclear ribonucleoprotein 13—to form C/D snoRNPs, the final product capable of performing Nm. 27 , 28 H/ACA-box snoRNA form a complex with dyskerin (Cbf5), Gar1, Nhp2, and Nop10 to guide pseudouridine. 29 To supplement the work of the snoRNPs, other auxiliary factors are used to efficiently assist in the process of maturing snoRNA and function.…”