Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Nucleic Acids Research logoLink to Nucleic Acids Research
. 2000 Jan 1;28(1):197–200. doi: 10.1093/nar/28.1.197

Non-coding, mRNA-like RNAs database Y2K

Volker A Erdmann, Maciej Szymanski 1, Abraham Hochberg 2, Nathan de Groot 2, Jan Barciszewski 1,a
PMCID: PMC102406  PMID: 10592224

Abstract

In last few years much data has accumulated on various non-translatable RNA transcripts that are synthesised in different cells. They are lacking in protein coding capacity and it seems that they work mainly or exclusively at the RNA level. All known non-coding RNA transcripts are collected in the database: http://www.man.poznan.pl/5SData/ncRNA/index.html

INTRODUCTION

Eukaryotic genes contain clearly identifiable open reading frames (ORFs) that direct the translation of functional proteins. However, not all RNA transcripts (other than tRNA, rRNA or snRNA) are translated into polypeptides. Many non-translatable mRNA-like RNA transcripts have been found in the cell. They are polyadenylated, spliced and are lacking long ORFs. It has been suggested that in the absence of protein product they function as RNA riboregulators and/or are involved in regulation of expression of linked genes. There is a wealth of data that RNA plays a variety of structural, informational, catalytic and regulatory roles in the cell.

CHARACTERISTICS OF NON-CODING RNA

These RNAs can be divided into the following classes:

• Gene regulators: Xist, roX1, Tsix, XistAS, roX2, H19, mei, LPW, KvDMR1, DGCR5, CMPD

• Abiotic stress signals: gadd7/adapt15, adapt33, hsrω, OxyR, DsrA, lbi, G90

• Biotic stress signals: His-1, ENOD40, CR20, GUT15

• Others: UHG, NTT, Bsr, BC1, BC200, SRA

Xist, roX RNAs

A subset of mammalian genes is subject to genomic imprinting. Three of them: Xist, H19 and IPW are known. The XIST/Xist gene is expressed exclusively from the inactive X-chromosome in somatic cells and produces an RNA of 17 kb in man and 15 kb in mouse. Multiple copies of Xist transgenes inserted into mouse chromosome 12 produced RNA transcript which coated the autosome, became hypoacetylated and late replicating. The developmental up-regulation is a consequence of the stabilisation of Xist RNA due to a promoter switch, which is an effect of hyperacetylation of chromatin upstream of Xist. Deacylation on the other hand leads to the further progression of X-inactivation (17). In Drosophila a mechanism of dosage compensation involves the products of the two genes roX1 and roX2 which do not encode proteins. roX1 RNA becomes associated with the X chromosome at sites determined by binding of the msl (male specific lethal) gene products (3). It has been shown that deleting a 65 kb region downstream of Xist results in constitutive expression and X-inactivation, implying the presence of a cis-regulatory element. In this region there is a gene Tsix antisense to Xist. It is a 40 kb RNA originating 15 kb downstream of Xist and transcribed across the Xist locus. Human Tsix RNA has no conserved ORFs, occurs exclusively in the nucleus and is localised at Xic, similarly to antisense Xist (XistAS) of mouse (8,9).

H19 RNA

The H19 gene codes for a capped, spliced and polyadenylated oncofetal 2.3 kb RNA. It is expressed exclusively from a maternal chromosome and is linked and co-regulated with the insulin-like growth factor 2 gene. The genes isolated from human and mouse consist of five exons separated by four unusually short introns. In the human sequence, there is a putative short ORF that would encode a 26 kDa protein, but no translation product has been identified so far. The evolutionarily conserved 42 bp element located upstream of the imprinting mark might play a role in imprinting and/or transcriptional regulation of H19. The G-rich repeat 1.5 kb upstream of mouse H19 was shown to be present in rats but absent in humans, and is not essential for H19 imprinting (1012).

IPW RNA

IPW has been mapped in the Prader–Willi syndrome region. The IPW (human) and ipw (mouse) RNA transcripts contain no long ORFs, are alternatively spliced and contain multiple copies of a 147 bp repeat arranged in a head-to-tail orientation. However unlike H19 and Xist, IPW is poorly conserved between mouse and human in both overall structure and nucleotide sequence. The region of similarity between mouse and human genes is restricted to a 500 bp region (1315).

DGCR5

DGCR5 is a gene from the DiGeorge syndrome region that codes for an untranslated RNA. It could be implicated in the control of expression of nearby genes (16).

KvDMR1

Loss of imprinting at IGF2 is associated with the cancer pre-disposition condition Beckwith–Wiedeman syndrome. Imprinting control elements are proposed to exist within the KvLQT1 locus. The KvDMR1-associated RNA is transcribed exclusively from the paternal allele and in the reverse orientation with respect to the maternally expressed KvLQT1 gene (17).

CMPD-associated RNA

Analysis of chromosomal translocations in patients with campomelic dysplasia (CMPD) suggested that disruption of genes in the 17q24–q25 region of chromosome 17 may be responsible for this disease that often involves sex reversal in genotypical males. Positional cloning allowed the identification and isolation of 3.5 kb cDNA which is specifically expressed in adult testis. There are no long ORFs detected in this RNA and no detectable protein produced in vitro (18).

Oxidative stress response RNAs (gadd7/adapt15, adapt33)

In mammals several groups of genes are expressed in response to UV irradiation or exposure to hydrogen peroxide and other reactive oxygen species. One of these genes, gadd7, is expressed in response to treatment with UV radiation. The gadd7 transcript is a 0.9 kb long polyadenylated RNA species, lacking long ORFs although there are three short ORFs for peptides of length 37, 38 and 43 amino acids. Other RNA species produced in response to oxidative stress, induced by hydrogen peroxide are adapt15 and adapt33. They have been isolated from Chinese hamster cells. Transcription products of both of these genes lack long ORFs and, similarly to gadd7 RNA, are polyadenylated. The adapt15 RNA is 0.95 kb long and is almost identical to gadd7 RNA, whereas for adapt33, two homologous RNA species of 1.46 and 0.99 kb have been isolated (1).

In addition, v-src end associated peptide 1 RNA (vseap1) shows high similarity to gadd7/adapt 15 RNA (19).

G90

The murine G90 gene has been identified by substractive hybridisation based on the differential presence of its transcript in large and small intestine. The full-length cDNA produces a 1.5 kb transcript that is polyadenylated but has no ORF larger than 248 bp. G90 is transcribed at very high levels in the small intestine and at lower levels in the large intestine, testis and kidney of the mouse (20).

OxyS RNA

In Escherichia coli an expression of hydrogen peroxide-inducible proteins is controlled by the transcriptional regulator, OxyR. It also induces the expression of an abundant 109 nt untranslated regulatory oxyS RNA. This RNA acts as a regulator of as many as 40 genes that integrate adaptation to hydrogen peroxide with other cellular stress responses and help to protect cells against oxidative damage. OxyS RNA can pair with a short sequence overlapping the Shine–Dalgarno sequence in the mRNA-encoding delta subunit of RNA polymerase (1,21).

DsrA RNA

The regulation of capsular polysaccharide synthesis in E.coli depends on the level of an unstable positive regulator, RcsA. The amount of RcsA protein is limited both by its rapid degradation and by its low level of protein synthesis. The last effect is due to transcriptional silencing by the histone-like protein H-NS. A small, 85 nt RNA, DsrA RNA, when overproduced activates transcription by counteracting H-NS silencing (1).

lbi RNA

The lbi (lipopolysaccharide biosynthesis interfering) RNA of phage Acm1, an untranslated RNA species of 97 nt, was shown to affect the biosynthesis of the O-specific polysaccharide of lipopolysaccharide (LPS) in various enterobacterial strains. Several lines of evidence suggested that lbi RNA may act in trans by an antisense-like mechanism regulating the activity of cellular target RNAs by formation of RNA hybrid molecules (22,23).

Heat shock response RNA (hsrω)

Protection against various environmental stresses is mainly conferred by the induction of heat shock genes. In Drosophila a major site of transcription in heat shock is the hsrω gene. If this gene is polyadenylated and spliced, the product RNA has only very small ORFs. The expression of hsrω is constitutive and is elevated by heat shock. In both normal and stressed cells the transcription from the hsrω locus gives rise to three transcripts ω1, ω2 and ω3. All of them have the same transcription start site. The hsrω1 transcript is ~10 kb long and results from transcription of the whole locus. At the 3′-end of hsrω1 transcript there is a 7–8 kb long region consisting of a short tandem repeat unit. The hsrω2 (~1.9 kb) transcript results from the use of an alternative polyadenylation site located just upstream of the tandem repeats region. The ω3 transcript (1.2–1.3 kb) is produced from the ω2 transcript by removal of a single intron and is a cytoplasmic species. This RNA does not contain any long ORFs. One of the short ORFs that is conserved in three Drosophila species would encode a peptide of length 23–27 amino acids (1).

His-1 RNA

Upon viral insertion in murine myeloid leukemias, the His-1 gene is activated. The His-1 gene is a single-copy sequence that has been found in a variety of vertebrate species. His-1 RNA is expressed as a 3 kb long, spliced and polyadenylated RNA. It lacks long ORFs. His-1 RNA transcription is correlated with viral insertion and carcinogenesis, since no transcripts have been detected in normal tissues. This finding suggests that the expression of the His-1 gene is highly restricted and that its inappropriate activation may contribute to carcinogenesis (1).

Brain specific RNAs (Bsr RNA, BC1 RNA, BC200 RNA)

Brain specific repetitive RNA (Bsr RNA) is a non-coding RNA that consists of tandem repeats of similar sequences, ~0.9 kb. Bsr RNA is preferentially expressed in the rat central nervous system (24).

BC1 RNA is generated by retroposition of tRNAAla. It is 120 nt long and is expressed preferentially in the brain by polymerase III. The sequence similarity between tRNAAla and the 5′ half of BC1 RNA is ~80%, however this domain does not fold in a tRNA like manner, but forms a stable stem–loop structure. The gene arose after mammalian radiation but prior to the diversification of the order Rodentia. The level of this RNA increases during the period of synaptogenesis. It plays a role in transport and translational regulation (25).

BC200 RNA is a small cytoplasmic non-coding RNA that has been identified in a number of primate species. Its expression is almost exclusively restricted to neural tissues. In the cell it is present as a ribonucleinoprotein particle. The gene encoding BC200 arose from a monomeric Alu element and the encoded RNA had been recruited into a function in the nervous system (26).

SRA RNA

SRA RNA, steroid receptor RNA activator, is selective for steroid hormone receptors and mediates transactivation via their N-terminal activation function. The transcript is 0.7–0.85 kb. It is a bona fide transcriptional coactivator selective for AF1 of steroid receptors. It is expressed as multiple isoforms in a cell-specific manner and is present in a steady-state coregulator complex with the AF2 coactivator SRC-1 (27).

MeiRNA

Fission yeast protein Mei2 is an RNA binding protein required for both premeiotic DNA synthesis and meiosis I. It binds to polyadenylated MeiRNA of ~0.5 kb, loss of which blocks meiosis I. It is required for nuclear localisation of Mei2 (28).

NTT RNA

NTT is human gene (non-coding transcript in T cells) which produces 17 kb non-coding, polyadenylated, but not spliced, nuclear RNA, expressed in activated CD4+ T cells. NTT has no ORF larger than 270 bp. There is a single copy of the NTT gene per haploid genome and both alleles are transcriptionally active (1).

UHG

Some small nucleolar RNAs (snoRNAs) are encoded within different introns of the unusually compact mammalian U22 host gene (UHG). U22 RNA is essential for the maturation of 18S rRNA. The U22 snoRNA gene lies within an intron of the single copy gene UHG which encodes a polyadenylated non-coding RNA. UHG RNAs in human and in mouse are 1114 and 590 nt long, respectively. Recently three other non-protein-coding snoRNA host genes: Gas5, U17HG and U19HG have been identified. Gas5 spliced RNA becomes polyadenylated and associates with translating ribosomes. Both the Gas5 and H17HG transcripts initiate with a cytosine followed by a pyrimidine-rich tract and belong to the 5′ terminal oligopyrimidine gene family (5′-TOP). U19HG after splicing remains in the nucleus and has a 5′ sequence reminiscent of 5′-TOP (29).

Early nodulin 40 (ENOD40)

Genes that are transcribed early in the plant–bacteria interaction (ENOD genes) are hypothesised to play a role in organogenesis and bacterial invasion. One of them, ENOD40, an early nodulin gene, is expressed following inoculation with Rhizobium meliloti or by adding nodulation factors or cytokinin to non-inoculated roots. ENOD40 encodes an RNA with a regulatory function and shows a very short ORF of only 10–13 amino acids (30,31).

Cytokinin response RNA (CR20)

The CR20 gene has been found to be one of several genes repressed by cytokinins. There are several CR20 transcripts generated by alternative splicing of the precursor RNA which do not contain a long ORF. A comparison of the two known CR20 sequences from cucumber and Arabidopsis thaliana has revealed a highly conserved 180 nt region that seems to form a stable secondary structure (1).

GUT 15 RNA

The tobacco genes with unstable transcripts (GUT) have been isolated and characterised. The GUT15 RNA is polyA+, contains at least one intron but does not contain a long ORF. It has a long segment similar to that of CR20 (32). Similar RNAs may also be present in aspen, poplar, soybean, rice and maize (A.van Hoof, personal communication).

Xlsirt RNA

Xlsirt RNAs have been identified as RNA species that are localised to the vegetal cortex of Xenopus oocytes during early stages of oogenesis. It has been proposed that they may play a structural role and may be used to localise other RNAs. Xlsirts form a family of heterogenous transcripts originating from both strands of the genes. The transcripts from one strand (sense strand) are localised in the vegetal cortex, while others are found throughout the cytoplasm. The transcripts contain 3–13 repeat units that are flanked by unique sequences (33,34).

Acknowledgments

ACKNOWLEDGEMENTS

We wish to thank Dr A.van Hoof for helpful comments. This work has been supported by the DFG (Gottfried Wilhelm Leibnitz Prize to V.A.E.), the SFB 344-C8, the DFG Trilateral Research Project Genomic Imprinting in Human Bladder Cancer and the Polish State Committee for Scientific Research.

REFERENCES

  • 1.Erdmann V.A., Szymanski,M., Hochberg,A., de Grot,N. and Barciszewski,J. (1999) Nucleic Acids Res., 27, 192–195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Brockdorf N. (1988) Curr. Opin. Genet. Dev., 8, 328–333. [DOI] [PubMed] [Google Scholar]
  • 3.Franke A. and Baker,B.S. (1999) Mol. Cell, 4, 117–122. [DOI] [PubMed] [Google Scholar]
  • 4.Chao Y.-C., Lee,S.-T., Chang,M.-C., Chen,H.-H., Chen,S.-S., Wu,T.-Y., Liu,F.-H., Hsu,E.-L. and Hou,R.F. (1998) J. Virol., 72, 2233–2245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Brockdorf N. and Duthie,S.M. (1998) Cell Mol. Life Sci., 54, 104–112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Duthie S.M., Nesterova,T.B., Formstone,E.J., Keohane,A.M., Turner,B.M., Zakian,S.M. and Brockdorf,N. (1999) Hum. Mol. Genet., 8, 195–204. [DOI] [PubMed] [Google Scholar]
  • 7.O’Neill L.P., Keokhane,A.M., Lavender,J.S., McCabe,V., Heard,E., Avner,P., Brockdorf,N. and Turner,B.M. (1999) EMBO J., 18, 2897–2907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Lee J.T., Davidov,L.S. and Varshawsky,D. (1999) Nature Genet., 21, 400–404. [DOI] [PubMed] [Google Scholar]
  • 9.Mise N., Goto,Y., Nakajima,N. and Takagi,N. (1999) Biochem. Biophys. Res. Commun., 258, 537–541. [DOI] [PubMed] [Google Scholar]
  • 10.Hurst L.D. and Smith,N.G.C. (1999) Trends Genet., 15, 134–135. [DOI] [PubMed] [Google Scholar]
  • 11.Frevel M.A.E., Hornberg,J.J. and Reeve,A.E. (1999) Trends Genet., 15, 216–218. [DOI] [PubMed] [Google Scholar]
  • 12.Stadnick M.P., Pieracci,F.M., Cranston,M.J., Taksel,E., Thorvaldsen,J.L. and Bartolomei,M.S. (1999) Dev. Genes Evol., 209, 239–248. [DOI] [PubMed] [Google Scholar]
  • 13.Tilgman S.M. (1999) Cell, 96, 185–193. [DOI] [PubMed] [Google Scholar]
  • 14.Brannan C.I. and Bartolomei,M. (1999) Curr. Opin. Genet. Dev., 9, 164–170. [DOI] [PubMed] [Google Scholar]
  • 15.Wevrick R. and Francke,U. (1997) Hum. Mol. Genet., 6, 325–332. [DOI] [PubMed] [Google Scholar]
  • 16.Southerland H.F., Wadey,R., McKie,J.M., Taylor,C., Atif,U., Johnstone,K.A., Halford,S., Kim,U.J., Goodship,J., Baldini,A. and Scambler,P.J. (1996) Am. J. Hum. Genet., 59, 23–31. [PMC free article] [PubMed] [Google Scholar]
  • 17.Smilinich N.J., Day,C.D., Fitzpatrick,G.V., Caldwell,G.M., Lossie,A.C., Cooper,P.R., Smallwood,A.C., Joyce,J.A., Schofield,P.N., Reik,W., Nicholls,R.D., Weksberg,R., Driscoll,D.J., Maher,E.R., Shows,T.B. and Higgins,M.J. (1999) Proc. Natl Acad. Sci. USA, 96, 8064–8069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Ninomiya S., Isomura,M., Narahara,K., Seino,Y. and Nakamara,Y. (1996) Hum. Mol. Genet., 5, 69–72. [DOI] [PubMed] [Google Scholar]
  • 19.Mizenina O., Yanushevich,Y., Musatkina,E., Rodina,A., Camonis,J., Tavitian,A. and Tatosyjan,A. (1998) FEBS Lett., 422, 79–84. [DOI] [PubMed] [Google Scholar]
  • 20.Krause R., Hemberger,M., Himmelbauer,H., Kalscheuer,V. and Fundele,R.H. (1999) Gene, 232, 35–42. [DOI] [PubMed] [Google Scholar]
  • 21.Gonzalez-Flecha B. and Demple,B. (1999) J. Bacteriol., 181, 3833–3836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Mammat U., Rietschel,E.T. and Schmidt,G. (1995) Mol. Microbiol., 15, 1115–1125. [DOI] [PubMed] [Google Scholar]
  • 23.Warnecke J.M., Moolenaar,C.E.C., Ritschel,E.Th., Hartmann,R.K. and Mamat,U. (1999) 4th Annual Meeting of the RNA Society, Edinburgh, Scotland: 23–27 June, Abstract 593.
  • 24.Komine Y., Tanaka,N.K., Yano,R., Takai,S., Yuasa,S., Shiiroishi,T., Tsuchiya,K. and Yamamori,T. (1999) Brain Res. Mol. Brain Res., 66, 1–13. [DOI] [PubMed] [Google Scholar]
  • 25.Brosius J. (1999) Gene, in press. [Google Scholar]
  • 26.Skryabin B.V., Kremerskothen,J., Vassilacopoulou,D., Disotell,T.R., Kapitonov,V.V., Jurka,J. and Brosius,J. (1998) J. Mol. Evol., 47, 677–685. [DOI] [PubMed] [Google Scholar]
  • 27.Lanz R.B., McKenna,N.J., Onate,S.A., Albrecht,U., Wong,J., Tsai,S.Y., Tsai,M.-J. and O’Malley,B.W. (1999) Cell, 97, 17–27. [DOI] [PubMed] [Google Scholar]
  • 28.Ohno M. and Mattaj,I.W. (1999) Curr. Biol., 9, R66–R69. [DOI] [PubMed] [Google Scholar]
  • 29.Weinstein L.B. and Steitz,J.A. (1999) Curr. Opin. Cell Biol., 11, 378–384. [DOI] [PubMed] [Google Scholar]
  • 30.Mirabella R., Martirani,L., Lamberti,A., Iaccarino,M. and Chiurazzi,M. (1999) Plant Mol. Biol., 39, 177–181. [DOI] [PubMed] [Google Scholar]
  • 31.Kouchi H., Takane,K., So,R.B., Ladha,J.K. and Reddy,P.M. (1999) Plant J., 18, 121–129. [DOI] [PubMed] [Google Scholar]
  • 32.van Hoff A., Kastenmayer,J.P., Crispin,B., Taylor,C.B. and Gree,P.J. (1995) Plant Gene Register Plant Physiol., 113, 1004. [Google Scholar]
  • 33.Kloc M., Spohr,G. and Etkin,L.D. (1993) Science, 262, 1712–1714. [DOI] [PubMed] [Google Scholar]
  • 34.Kloc M. and Etkin,L.D. (1994) Science, 265, 1101–1103. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES