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.
Highlights
Non-coding RNAs are involved in a multitude of cellular processes but the biochemical function of many small non-coding RNAs remains unclear
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
We have recently shown that stem-bulge RNAs (sbRNAs) from several nematode species can functionally substitute for vertebrate Y RNAs and support the initiation of chromosomal DNA replication in vitro, whereas CeY RNA does not (Kowalski et al, 2015)
Summary
In eukaryotes the biogenesis of Y RNAs begins in the nucleus, as RNA polymerase III transcription is terminated. The intracellular localisation of Y RNAs changes under conditions of cellular stress (Chen and Wolin, 2004) Both Ro60 and Y RNAs accumulate in the nucleus after UV irradiation or oxidative stress in several species (Chen et al, 2000, 2003; Sim et al, 2009, 2012). This has been demonstrated for the human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukaemia virus (Garcia et al, 2009; Wang et al, 2007) This process does not require Ro60 binding and likely occurs during early stages of Y RNA biogenesis when nascent Y RNAs are present in the nucleus (Wang et al, 2007). It remains to be seen whether the functional homology between vertebrate Y RNAs and nematode sbRNAs is reflected in a similar distribution of these nematode sbRNAs in the nuclear and cytoplasmic fractions of the cell
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