snoRNA-LBME-db, a comprehensive database of

human H/ACA and C/D box snoRNAs.

VERSION 2

Introduction
C/D box snoRNPs
H/ACA box snoRNPs
Cajal body-specific scaRNAs
Telomerase RNA
Expression of snoRNAs
SnoRNAs and genomic imprinting
Selected reviews


Introduction

This database of human C/D box and H/ACA modification guide RNAs is implemented at the Laboratoire de Biologie Moléculaire Eucaryote (LBME, CNRS and Université Paul Sabatier) in Toulouse, France, and maintained by Laurent Lestrade (Institut d'Exploration Fonctionnelle des Génomes) et Michel Weber (Laboratoire de Biologie Moléculaire Eucaryote). We thank our colleagues at the LBME for their help in constructing this database, and, in particular, Jean-Pierre Bachellerie for its compilation of snoRNA sequences.

Colleagues all around the world are encouraged to address their criticisms, remarks and corrections to

Information on a particular snoRNA can be accessed by three ways:

1- On the Search page, just type the name of the snoRNA (for example ACA17) in the Id window.
2- The Find guide RNA contains the sequences of the human ribosomal rRNAs 28S, 18S and 5.8S, and of the snRNAs U1, U2, U4, U5 and U6, with the positions of modified (2'O-ribose methylated or pseudo-uridinylated) nucleotides, and the identity of the corresponding modification guide RNAs. You can click on the name of the relevant snoRNA.
3- This database is linked to the UCSC Genome Browser. In the human genome Browser page, type the name of the snoRNA (for example ACA17) in the "Position" window, and click on Submit. You will be directed to the position of that snoRNA in the human genome. Clicking on ACA17 on the right hand part of the Browser screen will direct you to the corresponding page of the snoRNA-LBME-db.

The human rRNAs 28S, 18S and 5.8S carry together about 100 pseudouridines and 110 2'O-ribose methyl groups. These modifications are catalysed by two families of ribonucleoparticules, the H/CA box and C/D box snoRNPs, respectively. These two classes of snoRNPs are composed of a commun set of four proteins, and a small RNA that specifically guides the modification of one or two bases of the target RNA.

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C/D box snoRNPs


Figure from http://www.ergito.com/lookup.jsp?expt=kiss

The C/D box snoRNPs contain a commun set of four proteins: Fibrillarin (FBL, the methyltransferase), NOP56 (or NOL5A, nucleolar protein 5A), NOP5/NOP58 and NHPX (or NHP2L1, non-histone chromosome protein 2-like 1).

GeneLynx: FBL, NOL5A, NOP5/NOP58, NHP2L1

GeneCards: FBL, NOL5A, NOP5/NOP58, NHP2L1

The C/D box snoRNAs carry the conserved boxes C (RUGAUGA, R=purine) and D (CUGA) near their 5' and 3' ends, respectively. The two boxes are frequently folded together by a short (4-5 bp) terminal helix, to form a structure similar to a kink-turn. Often, imperfect copies of the C and D boxes, named C' and D', are located internally, in the order C/D'/C'/D. The 2'O-ribose methylation of target RNAs is guided by one or two 10-21 anti-sens elements located upstream of the D and/or D' boxes, so that the modified base is paired with the snoRNA nucleotide located precisely 5 nts upstream of the D or D' box.

 

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H/ACA box snoRNPs

The H/ACA box small nucleolar (sno)RNPs contain a commun set of four proteins: dyskerin (the pseudouridine synthase), GAR1 (nucleolar protein family A, member 1, NOLA1), NHP2 (NOLA2) and NOP10 (NOLA3).

GeneLynx: dyskerin, NOLA1, NOLA2, NOLA3

GeneCards: dyskerin, NOLA1, NOLA2, NOLA3

Figure from http://www.ergito.com/lookup.jsp?expt=kiss

The H/ACA box snoRNAs consist of two hairpins and two short single-stranded regions, which contain the H box (ANANNA) and the ACA box. The latter is always located 3 nts 5' of the 3' end of the snoRNA (see Figure 1). The hairpins contain bulges, or recognition loops, that form complex pseudo-knots with the target RNA, where the target uridine is the first unpaired base (see Figure). The position of the substrate uridine always resides 14-16 nts upstream of the H box (left recognition pocket) or of the ACA box (right recognition pocket). Some H/ACA box snoRNAs can thus guide the modification of two uridines, sometimes in two different rRNAs (U69, ACA10, ACA31). However, many H/ACA snoRNAs have only one identified target, and a growing number have none.

 


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Cajal body-specific scaRNAs

A new facet in H/ACA box small RNA's world emerged with the cloning of U85, a 330 nt-long RNA that contains both a C/D box and an H/ACA box domain. Accordingly, U85 can guide both the pseudouridylation of base U46 and the 2'O-ribose methylation of base C45 of the U5 snRNA. Subsequently, U85 was found to co-localize with coilin in Cajal bodies.

 

U85 was the first member of the so-called small Cajal body-specific (sca)RNAs. Other members have a C/D-H/ACA composite structure similar to that of U85 (U87, U88, U89), while others have only one (U92) or two (U93) H/ACA box domains. On the contrary, the scaRNAs U90 and U91 have the characteristic structure of classical C/D box snoRNAs. The scaRNAs share three properties:

1- they co-localize with coilin in Cajal bodies.

2- they can guide modifications of the RNA polymerase II-transcribed snRNAs (U1, U2, U4 and U5).

3- H/ACA box scaRNAs have one or two  Cajal body-specific localization signal, or CAB box (UGAG).

 

 

Reprinted from Henras, A.K., Dez, C. and Henry, Y. Current Opinion in Structural Biology 14:335-343 (2004), with permission from Elsevier.

 

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Telomerase RNA

The 3' most part of the human telomerase RNA (hTR or TERC)) folds into a characteristic H/ACA box snoRNA-like structure. Accordingly, hTR associates with the four core proteins of H/ACA box snoRNPs, dyskerin, and NOLA1-3. Moreover, this H/ACA domain contains a Cajal body-specific localization signal (CAB box), and localizes in Cajal bodies. Mutations in hTR gene are the cause of the autosomal dominant form of dyskeratosis congenita (OMIM#127550), while mutations in the dyskerin (DCK1) gene cause the X-linked form of the disease (OMIM#30500).

Expression of snoRNAs

         In vertebrates, sequences encoding H/ACA and C/D box snoRNAs and scaRNAs are generally located in introns of their host gene, in the same orientation. So far, an intron can carry only one snoRNA gene, but a host gene can carry several snoRNA genes in different introns. However, the human C/D box snoRNAs U3, U8, U13, mgU2-25/61 and mgU12-22/U4-8 are transcribed by RNA polII as independent units. Intronic snoRNAs are produced by exonucleolytic degradation of the debranched lariat after splicing, the stable part being protected by the binding of snoRNP core proteins, and/or of ancillary proteins, probably to the pre-mRNA.

The host genes of snoRNAs are either protein coding or non-coding, and often belong to the family of 5' TOP (5'-Terminal Oligo Pyrimidine tract) genes. Coding host genes include those of several ribosomal proteins, or proteins associated with ribosome biosynthesis or translation. Particularly interesting cases are the H/ACA box snoRNAs ACA36 and ACA56, that are located in introns of the gene encoding dyskerin (one of the four core proteins of H/ACA box snoRNPs). Similarly, the H/ACA box ACA51 and C/D box HBII-55 snoRNAs are located in the gene encoding NOP56/NOL5A (one of the four core proteins of C/D box snoRNPs). The C/D box snoRNA HBII-95 and HBII-234 are hosted by the gene encoding NOP5/NOP58 protein (one of the four core proteins of C/D box snoRNPs). However, many newly discovered snoRNAs reside in genes with quite diverse functions, or of unknown function.

Intriguing cases are the six H/ACA box snoRNAs ACA1, ACA8, ACA18, ACA25, ACA32 and ACA40, that reside in the RefSeq gene MGC5306. This gene encodes an hypothetical protein of 278 aa. As snoRNAs in this gene are more conserved than exons, its main function might be to produce snoRNAs rather than a protein. Similarly, the C/D box snoRNAs U22, U25, U26, U27, U28, U29, U30 and U31 reside in introns of the non-coding gene UHG (U22 host gene).

A growing number of snoRNAs have a tissue-specific expression, most probably reflecting that of the host gene. This is the case, for example, with the brain-specific H/ACA box snoRNA HBI-36, that is located in the gene encoding the serotonin receptor 5HT-2c.

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SnoRNAs and genomic imprinting

In the human and mouse genomes, two imprinted loci contain clusters of tandemly arranged snoRNAs. At the human 15q11-q13 locus (Prader-Willi/Angelman syndrome region, OMIM#176270, OMIM#105830), a very large (several hundreds of kb), maternally expressed and brain-specific gene contains 2 tandems of 42 and 29 highly related copies of C/D snoRNAs, HBII-52 and HBII-85. The human 14q32locus also contains a cluster of tandemly repeated, maternally expressed, C/D box snoRNAs. The role, if any, of these snoRNAs in genomic imprinting remains to be elucidated. However, the analysis of chromosomal translocations has reduced the minimal interval for the Prader-Willi/Angelman susceptibility region to a 121kb interval, in which the only known genes are those encoding the cluster of C/D box snoRNAs HBII-85 and the unique C/D box snoRNA HBII-438A (Gallagher et al.(2002) Am. J. Hum. Genet. 71:669-678).

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Selected reviews:

Pertinent original articles are given for each snoRNA in the data base. Here are some selected reviews:

- Bachellerie, J. P., Cavaille, J., and Huttenhofer, A. (2002). The expanding snoRNA world. Biochimie, 84, 775-790
- Filipowicz, W., and Pogacic, V. (2002). Biogenesis of small nucleolar ribonucleoproteins. Curr Opin Cell Biol, 14, 319-327.
- Kiss, T. (2001). Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs. Embo J, 20, 3617-3622.
- Kiss, T. (2002). Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell, 109, 145-148.
- Weinstein, L. B., and Steitz, J. A. (1999). Guided tours: from precursor snoRNA to functional snoRNP. Curr Opin Cell Biol, 11, 378-384.
- Henras, A. K., Dez, C., and Henry, Y. (2004). RNA structure and function in C/D and H/ACA s(no)RNPs. Curr Opin Struct Biol, 14, 335-343.
Last update: June 30 2016 13:45:56.