Elsevier

Biochimie

Volume 84, Issue 8, August 2002, Pages 775-790
Biochimie

Review
The expanding snoRNA world

https://doi.org/10.1016/S0300-9084(02)01402-5Get rights and content

Abstract

In eukaryotes, the site-specific formation of the two prevalent types of rRNA modified nucleotides, 2′-O-methylated nucleotides and pseudouridines, is directed by two large families of snoRNAs. These are termed box C/D and H/ACA snoRNAs, respectively, and exert their function through the formation of a canonical guide RNA duplex at the modification site. In each family, one snoRNA acts as a guide for one, or at most two modifications, through a single, or a pair of appropriate antisense elements. The two guide families now appear much larger than anticipated and their role not restricted to ribosome synthesis only. This is reflected by the recent detection of guides that can target other cellular RNAs, including snRNAs, tRNAs and possibly even mRNAs, and by the identification of scores of tissue-specific specimens in mammals. Recent characterization of homologs of eukaryotic modification guide snoRNAs in Archaea reveals the ancient origin of these non-coding RNA families and offers new perspectives as to their range of function.

Introduction

The biogenesis of eukaryotic ribosomes in the nucleolus involves an intricate series of pre-rRNA processing steps. This results in the removal of extended spacer regions from the primary transcript and production of stoichiometric amounts of mature small and large subunit rRNAs. Before its cleavage by endo- and exonucleases, the nascent pre-rRNA undergoes a complex pattern of nucleoside modifications of its mature small subunit (SSU) and large subunit (LSU) sequences. These modifications are of two prevalent types, 2-O-ribose methylation or pseudouridylation, each involving about 50–100 sites per eukaryotic ribosome 〚1〛, 〚2〛, 〚3〛. They are exclusively located within the most conserved, functionally important domains of mature RNAs, particularly into the structural elements contributing to the peptidyl-transfer region and its vicinity 〚4〛 and their positions are largely (but not perfectly) conserved among distant eukaryotes. While these modifications of elusive role are not absolutely essential, they are likely to fine-tune rRNA folding and interactions with ribosomal proteins, thereby modulating both the biogenesis and activity of the ribosomes. The two types of eukaryotic rRNA modifications are directed by two large families of snoRNAs (small nucleolar RNAs) which specify the sites to be modified, in both cases through the formation of a specific duplex at the rRNA modification site, while the catalytic function is provided by a common protein enzyme, methylase or pseudouridine synthase, associated with the snoRNA. Since a single snoRNA guide can direct one, or at most two rRNA modifications, the number of these RNA species was expected until recently to approach 200 in vertebrates.

However, recent studies show that the complexity of the two snoRNA guide families has been largely underestimated. Their diversity relates not only to their genetic organization and biosynthesis but also to the existence of variant snoRNA structures and multiple cellular RNA targets, reflecting a range of cellular functions beyond ribosome biogenesis. Novel members of the modification guide snoRNA families target spliceosomal snRNAs in vertebrates, tRNAs in Archaea and even probably eukaryotic mRNAs, in addition to rRNAs. Remarkably, an increasing number of “orphan” guides without known RNA targets have been identified. Several of them are expressed in a tissue-specific fashion and submitted to genomic imprinting, adding another level of complexity to the biological roles of snoRNA guides in mammals. Meanwhile, the identification of homologs of guide snoRNAs in organisms lacking a nucleus, Archaea, provides further insights into the evolutionary origin and function of these two large families of non-coding RNAs.

Fundamental properties of snoRNA guides for rRNA modification have been reviewed previously 〚2〛, 〚3〛, 〚5〛, 〚6〛, 〚7〛, 〚8〛, 〚9〛 and the reader is referred to these articles for further information on their gene organization, biogenesis and guide function, as well as to reviews dealing with pre-rRNA processing and nucleotide modification in eukaryotes 〚1〛, 〚10〛, 〚11〛, 〚12〛, 〚13〛. In this article, following an updated summary of the properties of rRNA modification guides, we will focus on recent breakthroughs revealing the unanticipated structural and functional diversity of the two families of guide snoRNAs in organisms ranging from Archaea to Eukarya.

Section snippets

Structure and function

Except for the RNA component for RNase MRP, all snoRNAs to date fall into two major classes, antisense box C/D and box H/ACA snoRNAs, based on the presence of short consensus sequence motifs 〚14〛. Most members of the two snoRNA families guide the 2′-O-ribose methylations and pseudouridylations, respectively, of rRNA. It is noteworthy, however, that a handful of them are involved instead in pre-rRNA cleavages 〚12〛. The two snoRNA guide families have been identified in a wide spectrum of eukaryal

Modification guides for spliceosomal snRNAs

Mammalian U1, U2, U4, U5 and U6 snRNAs contain a very substantial number of 2′-O-methylations and pseudouridylations, amounting collectively to 30 and 24, respectively 〚78〛. Interestingly, these modifications are mainly located in the snRNA segments involved in intermolecular RNA–RNA interactions or conformational switches during spliceosome assembly and function, suggesting that they play an important role in splicing control 〚78〛. In line with this notion, modifications in the 5′ terminal

Brain-specific snoRNAs and genomic imprinting

In contrast to all known rRNA or snRNA modification guides and unlike most orphan snoRNAs, an increasing number of recently identified snoRNAs, mostly of the C/D family, exhibit a tissue-specific expression pattern, being mainly expressed within the brain 〚106〛, 〚109〛, 〚110〛, 〚111〛, 〚112〛, 〚113〛. Intriguingly, the genes of all of them are subjected to genomic imprinting, an epigenetic phenomenon that restricts gene expression to only one chromosome, either the paternal or the maternal allele

Archaeal modification guides, tRNA targets and archaeal splicing

In contrast to eukaryotes, the rRNA of typical bacterium Escherichia coli contains only four 2′-O-methylations and 10 pseudouridines and each of these modifications appears to be catalyzed by a site-specific protein enzyme, ribose methylase or pseudouridine synthase, without any RNA cofactor 〚38〛, 〚122〛, 〚123〛. Among prokaryotic organisms, Archaea appear more closely related to Eukarya than to Bacteria by multiple aspects of the macromolecular machineries involved in DNA replication,

General conclusions

Methylation of 2′-hydroxyl groups may protect RNA from hydrolytic degradation, enhance hydrophobic surfaces and stabilize helical stems. Pseudouridines, through their flexible C–C glycosyl bonds and increased capacity, relative to uridines, to form H-bonds, may significantly contribute to RNA tertiary structure. Nucleotide modifications directed by snoRNA guides appear in most cases dispensable for cell viability or growth. However, they are likely to have an important biological role by

Acknowledgements

The work performed in J.P.B. laboratory was supported by laboratory funds from the Centre National de la Recherche Scientifique and Université Paul Sabatier, Toulouse, by grants from Association pour la Recherche sur le Cancer, the Toulouse Genopole and the Ministère de l’Education Nationale, de la Recherche et de la Technologie (Programme de Recherche Fondamentale en Microbiologie et Maladies Infectieuses et Parasitaires, 2001–2002) to J.P.B., and a grant from the Programme Interdisciplinaire

References (153)

  • F Barneche et al.

    Identification of 66 box C/D snoRNAs in Arabidopsis thaliana: extensive gene duplications generated multiple isoforms predicting new ribosomal RNA 2′-O-methylation sites

    J. Mol. Biol.

    (2001)
  • K.T. Tycowski et al.

    Non-coding snoRNA host genes in Drosophila: expression strategies for modification guide snoRNAs

    Eur. J. Cell. Biol.

    (2001)
  • Y. Xu et al.

    Expression studies on clustered trypanosomatid box C/D small nucleolar RNAs

    J. Biol. Chem.

    (2001)
  • D.A. Dunbar et al.

    Fibrillarin-associated box C/D small nucleolar RNAs in Trypanosoma brucei. Sequence conservation and implications for 2′-O-ribose methylation of rRNA

    J. Biol. Chem.

    (2000)
  • H. Bugl et al.

    RNA methylation under heat shock control

    Mol. Cell.

    (2000)
  • T. Caldas et al.

    Translational defects of Escherichia coli mutants deficient in the Um(2552) 23S ribosomal RNA methyltransferase RrmJ/FTSJ

    Biochem. Biophys. Res. Commun.

    (2000)
  • P. Ganot et al.

    Site-specific pseudouridine formation in preribosomal RNA is guided by small nucleolar RNAs

    Cell

    (1997)
  • J. Ni et al.

    Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal RNA

    Cell

    (1997)
  • J. Ofengand et al.

    Mapping to nucleotide resolution of pseudouridine residues in large subunit ribosomal RNAs from representative eukaryotes, prokaryotes, archaebacteria, mitochondria and chloroplasts

    J. Mol. Biol.

    (1997)
  • X.H. Liang et al.

    Identification of the first trypanosome H/ACA RNA that guides pseudouridine formation on rRNA

    J. Biol. Chem.

    (2001)
  • G. Chanfreau et al.

    Yeast RNase III as a key processing enzyme in small nucleolar RNAs metabolism

    J. Mol. Biol.

    (1998)
  • D. Filippini et al.

    U86, a novel snoRNA with an unprecedented gene organization in yeast

    Biochem. Biophys. Res. Commun.

    (2001)
  • M.H. Renalier et al.

    SnoRNA U21 is also intron-encoded in Drosophila melanogaster but in a different host-gene as compared to warm-blooded vertebrates

    FEBS Lett.

    (1996)
  • A. Niewmierzycka et al.

    S-Adenosylmethionine-dependent methylation in Saccharomyces cerevisiae. Identification of a novel protein arginine methyltransferase

    J. Biol. Chem.

    (1999)
  • D. Tollervey et al.

    Temperature-sensitive mutations demonstrate roles for yeast fibrillarin in pre-rRNA processing, pre-rRNA methylation, and ribosome assembly

    Cell

    (1993)
  • N.J. Watkins et al.

    A common core RNP structure shared between the small nucleolar box C/D RNPs and the spliceosomal U4 snRNP

    Cell

    (2000)
  • I. Vidovic et al.

    Crystal structure of the spliceosomal 15.5 kD protein bound to a U4 snRNA fragment

    Mol. Cell.

    (2000)
  • N.S. Heiss et al.

    Gene structure and expression of the mouse dyskeratosis congenita gene, dkc1

    Genomics

    (2000)
  • C. Hoang et al.

    Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme

    Cell

    (2001)
  • K.T. Tycowski et al.

    Modification of U6 spliceosomal RNA is guided by other small RNAs

    Mol. Cell.

    (1998)
  • A.G. Matera

    Nuclear bodies: multifaceted subdomains of the interchromatin space

    Trends Cell. Biol.

    (1999)
  • J.E. Sleeman et al.

    Newly assembled snRNPs associate with coiled bodies before speckles, suggesting a nuclear snRNP maturation pathway

    Curr. Biol.

    (1999)
  • J.M. Hughes

    Functional base-pairing interaction between highly conserved elements of U3 small nucleolar RNA and the small ribosomal subunit RNA

    J. Mol. Biol.

    (1996)
  • J.P. Bachellerie et al.

    Small nucleolar RNAs guide the ribose methylations of eukaryotic rRNAs

  • J. Ofengand et al.

    The pseudouridine residues of rRNA: number, location, biosynthesis and function

  • R. Brimacombe et al.

    Clustering of modified nucleotides at the functional center of bacterial ribosomal RNA

    Faseb. J.

    (1993)
  • T. Kiss et al.

    Characterization of the intron-encoded U19 RNA, a new mammalian small nucleolar RNA that is not associated with fibrillarin

    Mol. Cell. Biol.

    (1996)
  • J.P. Bachellerie et al.

    Nucleotide modifications of eukaryotic rRNAs: the world of small nucleolar RNAs revisited

  • J. Ofengand et al.

    The pseudouridine residues of ribosomal RNA

    Biochem. Cell. Biol.

    (1995)
  • B. Sollner-Webb et al.

    Ribosomal RNA processing in eukaryotes

  • E. Caffarelli et al.

    Processing of the intron-encoded U16 and U18 snoRNAs: the conserved C and D boxes control both the processing reaction and the stability of the mature snoRNA

    Embo. J.

    (1996)
  • T.S. Lange et al.

    Conserved boxes C and D are essential nucleolar localization elements of U14 and U8 snoRNAs

    Embo. J.

    (1998)
  • D.A. Samarsky et al.

    The snoRNA box C/D motif directs nucleolar targeting and also couples snoRNA synthesis and localization

    Embo. J.

    (1998)
  • T. Villa et al.

    Identification of a novel element required for processing of intron-encoded box C/D small nucleolar RNAs in Saccharomyces cerevisiae

    Mol. Cell. Biol.

    (2000)
  • Z. Kiss-Laszlo et al.

    Sequence and structural elements of methylation guide snoRNAs essential for site-specific ribose methylation of pre-rRNA

    Embo. J.

    (1998)
  • K.T. Tycowski et al.

    A mammalian gene with introns instead of exons generating stable RNA products

    Nature

    (1996)
  • J. Cavaille et al.

    Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA guides

    Nature

    (1996)
  • T.M. Lowe et al.

    A computational screen for methylation guide snoRNAs in yeast

    Science

    (1999)
  • L.H. Qu et al.

    Identification of 10 novel snoRNA gene clusters from Arabidopsis thaliana

    Nucl. Acids Res.

    (2001)
  • J.W. Brown et al.

    Multiple snoRNA gene clusters from Arabidopsis

    RNA

    (2001)
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