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.

Highlights

  • On several occasions, the fortuitous identification of RNAs with odd features turned out to be at the origin of a new family of non-coding RNAs

  • Human C/D snoRNAs could direct mRNA methylation and modulate the translation level of their target [206]. These data suggest that eukaryotic C/D small nucleolar ribonucleoproteins (snoRNPs) could perform functions outside their main sites of accumulation, i.e., the nucleolus and Cajalproteins body (CB), which was already suggested by the fact that scaRNAs exhibit small nuclear RNAs (snRNAs) modification activity in the nucleoplasm in the absence of CBs [207]

  • In a minority of cases, a molecular function has been found, such as eutherian snord115 that controls splicing and editing of a target mRNA [212,213,214] or the yeast snR4 and snR45 that guide ribosomal RNA (rRNA) acetylation [208]. The latter are interesting as it shows that the role of orphan snoRNAs could rely to conventional target. As it is true for other non-coding RNAs (ncRNAs), the snoRNA category is currently subjected to numerous and exciting developments despite its early discovery

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Summary

Introduction

The fortuitous identification of RNAs with odd features turned out to be at the origin of a new family of non-coding RNAs (ncRNAs). RNAs (scaRNAs) with similar features as snoRNAs and forming equivalent catalytic RNPs were found enriched in Cajal bodies (CBs, for a review, see [26]). In these nuclear bodies, some are the catalysts for ribose 20 -O-methylation and for pseudouridylation inside functionally important sequences of spliceosomal small nuclear RNAs (snRNAs) (for a review, see [27]). RNA-guided modification is not the prerogative of snoRNPs, and scaRNPs illustrated a potential of diversity towards substrate specialization depending on their nuclear localization Data accumulated this last decade added diversity to the pattern of expression, the place, the partners, and the functions of snoRNAs that could not still be perceived as confined to ribosome-associated functions. C/D and H/ACA snoRNAs, including in vivo knockout models, are available in recent reviews [15,28,29,30,31,32,33]

Molecular Features for the Canonical Paradigm of RNA-Guided Activity
10. Conclusions
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