Functional roles of non-coding Y RNAs

Abstract

Non-coding RNAs are involved in a multitude of cellular processes but the biochemical function of many small non-coding RNAs remains unclear. The family of small non-coding Y RNAs is conserved in vertebrates and related RNAs are present in some prokaryotic species. Y RNAs are also homologous to the newly identified family of non-coding stem-bulge RNAs (sbRNAs) in nematodes, for which potential physiological functions are only now emerging. Y RNAs are essential for the initiation of chromosomal DNA replication in vertebrates and, when bound to the Ro60 protein, they are involved in RNA stability and cellular responses to stress in several eukaryotic and prokaryotic species. Additionally, short fragments of Y RNAs have recently been identified as abundant components in the blood and tissues of humans and other mammals, with potential diagnostic value. While the number of functional roles of Y RNAs is growing, it is becoming increasingly clear that the conserved structural domains of Y RNAs are essential for distinct cellular functions. Here, we review the biochemical functions associated with these structural RNA domains, as well as the functional conservation of Y RNAs in different species. The existing biochemical and structural evidence supports a domain model for these small non-coding RNAs that has direct implications for the modular evolution of functional non-coding RNAs.

Keywords: DNA replication; Non-coding RNA; RNA domains; RNA stability; Y RNA.

Graphical abstract

Fig. 1

The non-coding human Y RNAs. The nucleotide sequences and secondary structures of hY RNAs are derived from sequence alignment and enzymatic and chemical probing (Teunissen et al., 2000, van Gelder et al., 1994). The conserved structural RNA domains and their associated functions are highlighted for each hY RNA. The size in nucleotides (nt) and molecular weight (kDa) of each RNA is indicated. See main text for references.

Fig. 2

Approximate number of publications per year relating to small non-coding RNA (left y-axis) and Y RNA (right y-axis), respectively. Data are the number of hits on a Thomson Reuters Web of Science topic search for the phrases ‘small non-coding RNA’ and ‘Y RNA’ (including ‘YRNA’, ‘RoRNP’, ‘Ro RNP’ and ‘Y5 RNA’ with white space characters).

Fig. 3

Modular structure of prokaryotic and eukaryotic Y RNAs. The overall secondary structures of the indicated RNAs are shown schematically and are based on consensus structures. Secondary structures in the divergent loop domains are omitted for clarity. RNA motifs acting as binding sites for Ro60 protein orthologues are shown in red. RNA motifs required for DNA replication are highlighted in blue, and interaction sites for the prokaryotic exonuclease PNPase are highlighted by a grey circle. See main text for references. (For interpretation of the references to color in this legend, the reader is referred to the web version of the article.)