Nucleic Acids Research

Nucleic Acids Research 2005 33(Database Issue):D121-D124; doi:10.1093/nar/gki081

This Article Abstract Print PDF (229K) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Commercial Re-use Guidelines for Open Access NAR Content Google Scholar Articles by Griffiths-Jones, S. Articles by Bateman, A. Search for Related Content PubMed PubMed Citation Articles by Griffiths-Jones, S. Articles by Bateman, A. Social Bookmarking          What's this?

Nucleic Acids Research, 2005, Vol. 33, Database issue D121-D124
© 2005, the authors
Nucleic Acids Research, Vol. 33, Database issue © Oxford University Press 2005; all rights reserved

Rfam: annotating non-coding RNAs in complete genomes

Sam Griffiths-Jones^*, Simon Moxon, Mhairi Marshall, Ajay Khanna¹, Sean R. Eddy¹ and Alex Bateman

The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK and ¹ Howard Hughes Medical Institute and Department of Genetics, Washington University School of Medicine, St Louis, MO 63108, USA

^* To whom correspondence should be addressed. Tel: +44 1223 834244; Fax: +44 1223 494919; Email: sgj{at}sanger.ac.uk

Received September 15, 2004; Revised and Accepted October 8, 2004

	ABSTRACT

TOP ABSTRACT INTRODUCTION RECENT DEVELOPMENTS NON-CODING RNAS IN COMPLETE... FUTURE CHALLENGES REFERENCES

 
Rfam is a comprehensive collection of non-coding RNA (ncRNA) families, represented by multiple sequence alignments and profile stochastic context-free grammars. Rfam aims to facilitate the identification and classification of new members of known sequence families, and distributes annotation of ncRNAs in over 200 complete genome sequences. The data provide the first glimpses of conservation of multiple ncRNA families across a wide taxonomic range. A small number of large families are essential in all three kingdoms of life, with large numbers of smaller families specific to certain taxa. Recent improvements in the database are discussed, together with challenges for the future. Rfam is available on the Web at http://www.sanger.ac.uk/Software/Rfam/ and http://rfam.wustl.edu/.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION RECENT DEVELOPMENTS NON-CODING RNAS IN COMPLETE... FUTURE CHALLENGES REFERENCES

 
Non-coding RNA (ncRNA) genes produce a functional RNA product instead of a translated protein. These products are components of some of the most important cellular machines, such as the ribosome (ribosomal RNAs), the spliceosome (U1, U2, U4, U5 and U6 RNAs) and the telomerase (telomerase RNA). The known repertoire of ncRNA cellular functions is expanding rapidly. Small nucleolar RNAs (snoRNAs) guide essential modifications of ribosomal and spliceosomal RNAs [reviewed in (1)]. Ribozymes catalyse a range of reactions, such as self-cleavage of hepatitis delta virus transcripts, and 5' maturation of transfer RNAs (tRNAs) by the ubiquitous RNase P. A class of small RNAs almost unknown before 2000, the microRNAs (miRNAs), are found to be involved in regulation of ever more processes in higher eukaryotes—including development, cell death and fat metabolism—by repressing the translation of mRNA targets [reviewed in (2)]. Similar mRNA-binding regulatory roles in bacteria are fulfilled by distinct families of small RNAs [reviewed in (3)].

Like protein-coding genes, ncRNA sequences can be grouped into families and much can be learnt about structure and function from multiple sequence alignments of such families. Unlike proteins, ncRNAs often conserve a base-paired secondary structure with low primary sequence similarity. The combined secondary structure and primary sequence profile of a multiple sequence alignment of ncRNAs can be captured by statistical models, called profile stochastic context-free grammars (SCFGs), analogous to profile hidden Markov models (HMMs) of protein alignments.

Rfam is a database of ncRNA families represented by multiple sequence alignments and profile SCFGs, available via the Web at http://www.sanger.ac.uk/Software/Rfam/ and http://rfam.wustl.edu/. All the data are also available for download, local installation and sequence searching using the INFERNAL software package (http://infernal.wustl.edu/) (4). The Rfam/INFERNAL model is much like the Pfam/HMMER system (5), extended to deal with RNA secondary structure consensus, and has been discussed previously (6). Here, we concentrate on recent improvements and discuss challenges that we expect to address through future development.

	RECENT DEVELOPMENTS

TOP ABSTRACT INTRODUCTION RECENT DEVELOPMENTS NON-CODING RNAS IN COMPLETE... FUTURE CHALLENGES REFERENCES

 
The database has grown dramatically over the past two years: from 25 families annotating around 55 000 regions in the nucleotide sequences databases in release 1.0, to 379 families annotating over 280 000 regions in release 6.1. This growth is partly due to a significant increase in scope. The evolution of some large gene families, such as miRNAs and snoRNAs, is constrained partially by inter-molecular base-pairing, and thus they do not conserve significant sequence or secondary structure. While we cannot therefore represent all C/D box snoRNAs, or all miRNAs, with a single alignment and model, subfamilies are conserved and are now well represented in the database. Rfam also now includes not only bona fide ncRNA genes, but also structured regions of mRNA transcripts. These fall into two broad classes: self-splicing introns and cis-regulatory elements in the untranslated regions (UTRs). The latter can be used as detectors for a wide range of environmental conditions [e.g. bacterial riboswitches bind a range of metabolites as reviewed previously (7,8), and the 5'-UTR of the PrfA acts as a temperature-dependent switch (9)] to regulate message stability or translational efficiency.

This increased scope has led to the introduction of a limited type ontology, with the top-level types representing the three classes of structured RNA discussed above—‘Gene’, ‘Intron’ and ‘Cis-reg’. The database currently contains 308 gene families, 69 cis-regulatory elements and two self-splicing introns. The type field provides one of the primary entry points for family browsing and searching, enabling the user to quickly identify all snoRNA gene families for instance, or to find all riboswitches in the database.

One of the primary uses of the Rfam database is to search for homologues of known RNAs in a query sequence, including a complete genome. Indeed, the profile SCFG library has been used to annotate a number of newly sequenced genomes [e.g. Caenorhabditis briggsae (10), chicken (11) and Erwinia caratova (12)]. In addition, we calculate hits in over 200 complete genomes and chromosomes. These data are available through the web interface and are discussed briefly in the following section.

	NON-CODING RNAS IN COMPLETE GENOMES

TOP ABSTRACT INTRODUCTION RECENT DEVELOPMENTS NON-CODING RNAS IN COMPLETE... FUTURE CHALLENGES REFERENCES

 
Rfam makes available annotation of over 13 400 candidate ncRNA genes (plus 172 self-splicing introns and 1285 cis-regulatory RNA elements) belonging to 172 families in 224 completed chromosomes and genomes. The average bacterial genome contains over 80 hits, dominated by the number of tRNAs. A total of 170 regions are annotated in Escherichia coli, in which most experimental validation of computationally predicted ncRNAs has been carried out. Rfam annotated regions in Bacillus genomes (B.anthracis is shown in Figure 1) include a number of recently described riboswitches (7,8).

View larger version (43K): [in this window] [in a new window]   Figure 1. Rfam genome page for Bacillus anthracis. The table contains a summary of the number of members of each Rfam family in the genome, with the distribution of hits shown on the map.

 
These data provide the first comprehensive view of the distribution of ncRNAs in the three kingdoms of life. There are a small number of very large families representing some of the best-understood RNAs. Figure 2 shows that these few large families are the only RNAs that are ubiquitous between all three domains of life—only the essential translation components, tRNA and ribosomal RNA, together with RNase P (tRNA maturation) and SRP RNA (protein export) are found in eukaryotes, bacteria and archaea. It is tempting to believe that very few families will be added to the catalogue of universally conserved RNAs. However, it is clear that members of some families are highly divergent so as to be computationally almost unrecognizable. For example, although most eukaryotes would be expected to have a telomerase RNA, current computational techniques are unable to identify homologues in even well-studied model organisms such as Caenorhabditis elegans.

View larger version (23K): [in this window] [in a new window]   Figure 2. Taxonomic distribution of Rfam family members in the three kingdoms of life.

 
Only snoRNAs are found in eukaryotes and archaea and not in bacteria, but RNA families have not yet been identified that are common to bacteria and archaea but not eukaryotes, or eukaryotes and bacteria but not archaea. The vast majority of Rfam families are small, and are often specific to one taxonomic group, and in some cases to one organism, suggesting relatively recent evolution of function or divergence beyond our ability to recognize homologues. Many novel bacterial ncRNAs have been identified by a number of recent computational screens in E.coli [reviewed in (13)], but comparatively few have been experimentally verified. Rfam contains more than 30 ncRNA families based on the verified genes. Few large-scale studies have been conducted in archaea or eukaryotes, and it is clear that such efforts will identify many more small families.

	FUTURE CHALLENGES

TOP ABSTRACT INTRODUCTION RECENT DEVELOPMENTS NON-CODING RNAS IN COMPLETE... FUTURE CHALLENGES REFERENCES

 
Profile SCFG searches are computationally expensive. Rfam at present uses a BLAST-based heuristic (14) as described previously (6), reducing the search space with an inevitable sensitivity cost. This allows us to search a 5 Mb bacterial genome against the entire Rfam library in 24 h. Annotation of large eukaryotic genomes is just feasible using this approach. Recent advances allow the speed of profile SCFGs to be increased by a factor of 100 for most families, and provably do not reduce the sensitivity of the full SCFG search (15). Work is ongoing to incorporate such algorithms into the Rfam/INFERNAL approach. We also recognize that the current approach is restricted to RNAs with defined secondary structures, precluding inclusion of important families of essentially unstructured RNAs like XIST (X-Inactive Specific Transcript), RoX (RNA on X) and IPW (Imprinted in Prader–Willi). Furthermore, the consensus structure annotation may conceal additional elements in divergent structures. We plan to evaluate how the use of profile HMMs may allow the detection of homologues of unstructured RNAs, and investigate the propagation of structure annotation at the sequence level.

Perhaps the biggest challenge for annotation of higher eukaryotic genomes is the problem of ncRNA-derived pseudogenes and repeats. For example, the B2 repeat in mouse is evolutionarily related to a tRNA, and Alu repeats in human derive from SRP RNA (16). Over 10% of the draft human genome sequence is made up of 1.1 million Alu sequences (17), and there are over 350 000 B2 repeat sequences in mouse (18). The human genome also contains over 1000 sequences that are closely related to U6 spliceosomal RNA, yet sensible estimates of the U6 gene count suggest that <50 are functional. Other problem families include the polIII transcribed Y and 7SK RNAs. Distinguishing the functional copies from the large numbers of pseudogenes is an unsolved problem and presents a significant challenge to RNA computational biologists.

It seems likely that computational and experimental screens will continue to identify numerous novel ncRNAs. Most of these genes are predicted to fall into small families with narrow taxonomic ranges. In contrast, we believe that very few universally conserved RNAs will be found, and the large, well-studied and ubiquitous families will continue to make up the large majority of ncRNAs in a single genome. Rfam will continue to translate novel discoveries of ncRNA genes into alignments and models that are immediately useful for genome annotation and phylogenetic analysis.

	ACKNOWLEDGEMENTS

 
We thank all those who have contributed data and annotation and developed tools and algorithms for ncRNA detection, alignment and structure prediction. Work at the Sanger Institute is funded by the Wellcome Trust. A.K. and S.R.E. are supported by the Howard Hughes Medical Institute, the NIH National Human Genome Research Institute and Alvin Goldfarb.

	Notes

 
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use permissions, please contact journals.permissions{at}oupjournals.org.

	REFERENCES

TOP ABSTRACT INTRODUCTION RECENT DEVELOPMENTS NON-CODING RNAS IN COMPLETE... FUTURE CHALLENGES REFERENCES

 

1. Bachellerie,J.P., Cavaille,J. and Huttenhofer,A. ( (2002) ) The expanding snoRNA world. Biochimie, , 84, , 775–790.[Medline] .

2. Bartel,D.P. ( (2004) ) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, , 116, , 281–297.[CrossRef][Web of Science][Medline] .

3. Storz,G., Opdyke,J.A. and Zhang,A. ( (2004) ) Controlling mRNA stability and translation with small, noncoding RNAs. Curr. Opin. Microbiol., , 7, , 140–144.[CrossRef][Web of Science][Medline] .

4. Eddy,S.R. ( (2002) ) A memory-efficient dynamic programming algorithm for optimal alignment of a sequence to an RNA secondary structure. BMC Bioinformatics, , 3, , 18.[CrossRef][Medline] .

5. Bateman,A., Coin,L., Durbin,R., Finn,R.D., Hollich,V., Griffiths-Jones,S., Khanna,A., Marshall,M., Moxon,S., Sonnhammer,E.L. et al. ( (2003) ) The Pfam protein families database. Nucleic Acids Res., , 32, , D138–D141. .

6. Griffiths-Jones,S., Bateman,A., Marshall,M., Khanna,A. and Eddy,S.R. ( (2003) ) Rfam: an RNA family database. Nucleic Acids Res., , 31, , 439–441.[Abstract/Free Full Text] .

7. Mandal,M. and Breaker,R.R. ( (2004) ) Gene regulation by riboswitches. Nature Rev. Mol. Cell. Biol., , 5, , 451–463.[CrossRef][Web of Science][Medline] .

8. Vitreschak,A.G., Rodionov,D.A., Mironov,A.A. and Gelfand,M.S. ( (2004) ) Riboswitches: the oldest mechanism for the regulation of gene expression? Trends Genet., , 20, , 44–50.[CrossRef][Web of Science][Medline] .

9. Johansson,J., Mandin,P., Renzoni,A., Chiaruttini,C., Springer,M. and Cossart,P. ( (2002) ) An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes. Cell, , 110, , 551–561.[CrossRef][Web of Science][Medline] .

10. Stein,L.D., Bao,Z., Blasiar,D., Blumenthal,T., Brent,M.R., Chen,N., Chinwalla,A., Clarke,L., Clee,C., Coghlan,A. et al. ( (2003) ) The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics. PLoS Biol., , 1, , E45.[Medline] .

11. International Chicken Genome Sequencing Consortium ( (2004) ) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature, , in press. .

12. Bell,K.S., Sebaihia,M., Pritchard,L., Holden,M.T., Hyman,L.J., Holeva,M.C., Thomson,N.R., Bentley,S.D., Churcher,L.J., Mungall,K. et al. ( (2004) ) Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors. Proc. Natl Acad. Sci. USA, , 101, , 11105–11110.[Abstract/Free Full Text] .

13. Hershberg,R., Altuvia,S. and Margalit,H. ( (2003) ) A survey of small RNA-encoding genes in Escherichia coli. Nucleic Acids Res., , 31, , 1813–1820.[Abstract/Free Full Text] .

14. Altschul,S.F., Madden,T.L., Schaffer,A.A., Zhang,J., Zhang,Z., Miller,W. and Lipman,D.J. ( (1997) ) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res., , 25, , 3389–3402.[Abstract/Free Full Text] .

15. Weinberg,Z. and Ruzzo,W.L. ( (2004) ) Exploiting conserved structure for faster annotation of non-coding RNAs without loss of accuracy. Bioinformatics, , 20, , I334–I341. .

16. Weiner,A.M., Deininger,P.L. and Efstratiadis,A. ( (1986) ) Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu. Rev. Biochem., , 55, , 631–661.[CrossRef][Web of Science][Medline] .

17. International Human Genome Sequencing Consortium ( (2001) ) Initial sequencing and analysis of the human genome. Nature, , 409, , 860–921.[CrossRef][Medline] .

18. Mouse Genome Sequencing Consortium ( (2002) ) Initial sequencing and comparative analysis of the mouse genome. Nature, , 420, , 520–562.[CrossRef][Medline] .

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				T.-H. Chang, H.-D. Huang, L.-C. Wu, C.-T. Yeh, B.-J. Liu, and J.-T. Horng Computational identification of riboswitches based on RNA conserved functional sequences and conformations RNA, July 1, 2009; 15(7): 1426 - 1430. [Abstract] [Full Text] [PDF]

				S. J. Schroeder Advances in RNA Structure Prediction from Sequence: New Tools for Generating Hypotheses about Viral RNA Structure-Function Relationships J. Virol., July 1, 2009; 83(13): 6326 - 6334. [Full Text] [PDF]

				C. Schmeisser, H. Liesegang, D. Krysciak, N. Bakkou, A. Le Quere, A. Wollherr, I. Heinemeyer, B. Morgenstern, A. Pommerening-Roser, M. Flores, et al. Rhizobium sp. Strain NGR234 Possesses a Remarkable Number of Secretion Systems Appl. Envir. Microbiol., June 15, 2009; 75(12): 4035 - 4045. [Abstract] [Full Text] [PDF]

				C. Jogler, W. Lin, A. Meyerdierks, M. Kube, E. Katzmann, C. Flies, Y. Pan, R. Amann, R. Reinhardt, and D. Schuler Toward Cloning of the Magnetotactic Metagenome: Identification of Magnetosome Island Gene Clusters in Uncultivated Magnetotactic Bacteria from Different Aquatic Sediments Appl. Envir. Microbiol., June 15, 2009; 75(12): 3972 - 3979. [Abstract] [Full Text] [PDF]

				Y. Tabei and K. Asai A local multiple alignment method for detection of non-coding RNA sequences Bioinformatics, June 15, 2009; 25(12): 1498 - 1505. [Abstract] [Full Text] [PDF]

				A. Marchais, M. Naville, C. Bohn, P. Bouloc, and D. Gautheret Single-pass classification of all noncoding sequences in a bacterial genome using phylogenetic profiles Genome Res., June 1, 2009; 19(6): 1084 - 1092. [Abstract] [Full Text] [PDF]

				K. D. Passalacqua, A. Varadarajan, B. D. Ondov, D. T. Okou, M. E. Zwick, and N. H. Bergman Structure and Complexity of a Bacterial Transcriptome J. Bacteriol., May 15, 2009; 191(10): 3203 - 3211. [Abstract] [Full Text] [PDF]

				D. L. Kolbe and S. R. Eddy Local RNA structure alignment with incomplete sequence Bioinformatics, May 15, 2009; 25(10): 1236 - 1243. [Abstract] [Full Text] [PDF]

				L. Childs, Z. Nikoloski, P. May, and D. Walther Identification and classification of ncRNA molecules using graph properties Nucleic Acids Res., May 1, 2009; 37(9): e66 - e66. [Abstract] [Full Text] [PDF]

				B. P. Mello, E. F. Abrantes, C. H. Torres, A. Machado-Lima, R. d. S. Fonseca, D. M. Carraro, R. R. Brentani, L. F. L. Reis, and H. Brentani No-match ORESTES explored as tumor markers Nucleic Acids Res., May 1, 2009; 37(8): 2607 - 2617. [Abstract] [Full Text] [PDF]

				C.-L. Chen, H. Zhou, J.-Y. Liao, L.-H. Qu, and L. Amar Genome-wide evolutionary analysis of the noncoding RNA genes and noncoding DNA of Paramecium tetraurelia RNA, April 1, 2009; 15(4): 503 - 514. [Abstract] [Full Text] [PDF]

				J. Hertel, D. de Jong, M. Marz, D. Rose, H. Tafer, A. Tanzer, B. Schierwater, and P. F. Stadler Non-coding RNA annotation of the genome of Trichoplax adhaerens Nucleic Acids Res., April 1, 2009; 37(5): 1602 - 1615. [Abstract] [Full Text] [PDF]

				M. Hamada, H. Kiryu, K. Sato, T. Mituyama, and K. Asai Prediction of RNA secondary structure using generalized centroid estimators Bioinformatics, February 15, 2009; 25(4): 465 - 473. [Abstract] [Full Text] [PDF]

				T. Lassmann, O. Frings, and E. L. L. Sonnhammer Kalign2: high-performance multiple alignment of protein and nucleotide sequences allowing external features Nucleic Acids Res., February 1, 2009; 37(3): 858 - 865. [Abstract] [Full Text] [PDF]

				K. Morita, Y. Saito, K. Sato, K. Oka, K. Hotta, and Y. Sakakibara Genome-wide searching with base-pairing kernel functions for noncoding RNAs: computational and expression analysis of snoRNA families in Caenorhabditis elegans Nucleic Acids Res., February 1, 2009; 37(3): 999 - 1009. [Abstract] [Full Text] [PDF]

				D. A. Rodionov, P. Hebbeln, A. Eudes, J. ter Beek, I. A. Rodionova, G. B. Erkens, D. J. Slotboom, M. S. Gelfand, A. L. Osterman, A. D. Hanson, et al. A Novel Class of Modular Transporters for Vitamins in Prokaryotes J. Bacteriol., January 1, 2009; 191(1): 42 - 51. [Abstract] [Full Text] [PDF]

				K. D. Pruitt, T. Tatusova, W. Klimke, and D. R. Maglott NCBI Reference Sequences: current status, policy and new initiatives Nucleic Acids Res., January 1, 2009; 37(suppl_1): D32 - D36. [Abstract] [Full Text] [PDF]

				T. Mituyama, K. Yamada, E. Hattori, H. Okida, Y. Ono, G. Terai, A. Yoshizawa, T. Komori, and K. Asai The Functional RNA Database 3.0: databases to support mining and annotation of functional RNAs Nucleic Acids Res., January 1, 2009; 37(suppl_1): D89 - D92. [Abstract] [Full Text] [PDF]

				G. H. Jacobs, A. Chen, S. G. Stevens, P. A. Stockwell, M. A. Black, W. P. Tate, and C. M. Brown Transterm: a database to aid the analysis of regulatory sequences in mRNAs Nucleic Acids Res., January 1, 2009; 37(suppl_1): D72 - D76. [Abstract] [Full Text] [PDF]

				P. P. Chan and T. M. Lowe GtRNAdb: a database of transfer RNA genes detected in genomic sequence Nucleic Acids Res., January 1, 2009; 37(suppl_1): D93 - D97. [Abstract] [Full Text] [PDF]

				T. B. K. Reddy, R. Riley, F. Wymore, P. Montgomery, D. DeCaprio, R. Engels, M. Gellesch, J. Hubble, D. Jen, H. Jin, et al. TB database: an integrated platform for tuberculosis research Nucleic Acids Res., January 1, 2009; 37(suppl_1): D499 - D508. [Abstract] [Full Text] [PDF]

				T. Abe, T. Ikemura, Y. Ohara, H. Uehara, M. Kinouchi, S. Kanaya, Y. Yamada, A. Muto, and H. Inokuchi tRNADB-CE: tRNA gene database curated manually by experts Nucleic Acids Res., January 1, 2009; 37(suppl_1): D163 - D168. [Abstract] [Full Text] [PDF]

				D. Gerlach, E. V. Kriventseva, N. Rahman, C. E. Vejnar, and E. M. Zdobnov miROrtho: computational survey of microRNA genes Nucleic Acids Res., January 1, 2009; 37(suppl_1): D111 - D117. [Abstract] [Full Text] [PDF]

				A. Shulman-Peleg, R. Nussinov, and H. J. Wolfson RsiteDB: a database of protein binding pockets that interact with RNA nucleotide bases Nucleic Acids Res., January 1, 2009; 37(suppl_1): D369 - D373. [Abstract] [Full Text] [PDF]

				P. P. Gardner, J. Daub, J. G. Tate, E. P. Nawrocki, D. L. Kolbe, S. Lindgreen, A. C. Wilkinson, R. D. Finn, S. Griffiths-Jones, S. R. Eddy, et al. Rfam: updates to the RNA families database Nucleic Acids Res., January 1, 2009; 37(suppl_1): D136 - D140. [Abstract] [Full Text] [PDF]

				J. R. Cole, Q. Wang, E. Cardenas, J. Fish, B. Chai, R. J. Farris, A. S. Kulam-Syed-Mohideen, D. M. McGarrell, T. Marsh, G. M. Garrity, et al. The Ribosomal Database Project: improved alignments and new tools for rRNA analysis Nucleic Acids Res., January 1, 2009; 37(suppl_1): D141 - D145. [Abstract] [Full Text] [PDF]

				H.-Y. Huang, H.-Y. Chang, C.-H. Chou, C.-P. Tseng, S.-Y. Ho, C.-D. Yang, Y.-W. Ju, and H.-D. Huang sRNAMap: genomic maps for small non-coding RNAs, their regulators and their targets in microbial genomes Nucleic Acids Res., January 1, 2009; 37(suppl_1): D150 - D154. [Abstract] [Full Text] [PDF]

				N. K. Mimouni, R. B. Lyngso, S. Griffiths-Jones, and J. Hein An Analysis of Structural Influences on Selection in RNA Genes Mol. Biol. Evol., January 1, 2009; 26(1): 209 - 216. [Abstract] [Full Text] [PDF]

				V. Kunin, A. Copeland, A. Lapidus, K. Mavromatis, and P. Hugenholtz A Bioinformatician's Guide to Metagenomics Microbiol. Mol. Biol. Rev., December 1, 2008; 72(4): 557 - 578. [Abstract] [Full Text] [PDF]

				J. Daub, P. P. Gardner, J. Tate, D. Ramskold, M. Manske, W. G. Scott, Z. Weinberg, S. Griffiths-Jones, and A. Bateman The RNA WikiProject: Community annotation of RNA families RNA, December 1, 2008; 14(12): 2462 - 2464. [Abstract] [Full Text] [PDF]

				M. Abraham, O. Dror, R. Nussinov, and H. J. Wolfson Analysis and classification of RNA tertiary structures RNA, November 1, 2008; 14(11): 2274 - 2289. [Abstract] [Full Text] [PDF]

				N. C. Sheffield, H. Song, S. L. Cameron, and M. F. Whiting A Comparative Analysis of Mitochondrial Genomes in Coleoptera (Arthropoda: Insecta) and Genome Descriptions of Six New Beetles Mol. Biol. Evol., November 1, 2008; 25(11): 2499 - 2509. [Abstract] [Full Text] [PDF]

				Z. Huang, Y. Wu, J. Robertson, L. Feng, R. L. Malmberg, and L. Cai Fast and accurate search for non-coding RNA pseudoknot structures in genomes Bioinformatics, October 15, 2008; 24(20): 2281 - 2287. [Abstract] [Full Text] [PDF]

				T. Lu, S. Yu, D. Fan, J. Mu, Y. Shangguan, Z. Wang, Y. Minobe, Z. Lin, and B. Han Collection and Comparative Analysis of 1888 Full-length cDNAs from Wild Rice Oryza rufipogon Griff. W1943 DNA Res, October 1, 2008; 15(5): 285 - 295. [Abstract] [Full Text] [PDF]

				M. Rabani, M. Kertesz, and E. Segal Computational prediction of RNA structural motifs involved in posttranscriptional regulatory processes PNAS, September 30, 2008; 105(39): 14885 - 14890. [Abstract] [Full Text] [PDF]

				C. B. Do, C.-S. Foo, and S. Batzoglou A max-margin model for efficient simultaneous alignment and folding of RNA sequences Bioinformatics, July 1, 2008; 24(13): i68 - i76. [Abstract] [Full Text] [PDF]

				V. Knudsen and G. Caetano-Anolles NOBAI: a web server for character coding of geometrical and statistical features in RNA structure Nucleic Acids Res., July 1, 2008; 36(suppl_2): W85 - W90. [Abstract] [Full Text] [PDF]

				T.-H. Chang, J.-T. Horng, and H.-D. Huang RNALogo: a new approach to display structural RNA alignment Nucleic Acids Res., July 1, 2008; 36(suppl_2): W91 - W96. [Abstract] [Full Text] [PDF]

				L. Barquist and I. Holmes xREI: a phylo-grammar visualization webserver Nucleic Acids Res., July 1, 2008; 36(suppl_2): W65 - W69. [Abstract] [Full Text] [PDF]

				S. Mitra, I. V. Shcherbakova, R. B. Altman, M. Brenowitz, and A. Laederach High-throughput single-nucleotide structural mapping by capillary automated footprinting analysis Nucleic Acids Res., June 1, 2008; 36(11): e63 - e63. [Abstract] [Full Text] [PDF]

				P. Larsson, A. Hinas, D. H. Ardell, L. A. Kirsebom, A. Virtanen, and F. Soderbom De novo search for non-coding RNA genes in the AT-rich genome of Dictyostelium discoideum: Performance of Markov-dependent genome feature scoring Genome Res., June 1, 2008; 18(6): 888 - 899. [Abstract] [Full Text] [PDF]

				A. Wilm, D. G. Higgins, and C. Notredame R-Coffee: a method for multiple alignment of non-coding RNA Nucleic Acids Res., May 1, 2008; 36(9): e52 - e52. [Abstract] [Full Text] [PDF]

				C. Jochl, M. Rederstorff, J. Hertel, P. F. Stadler, I. L. Hofacker, M. Schrettl, H. Haas, and A. Huttenhofer Small ncRNA transcriptome analysis from Aspergillus fumigatus suggests a novel mechanism for regulation of protein synthesis Nucleic Acids Res., May 1, 2008; 36(8): 2677 - 2689. [Abstract] [Full Text] [PDF]

				E. A. Glazov, S. McWilliam, W. C. Barris, and B. P. Dalrymple Origin, Evolution, and Biological Role of miRNA Cluster in DLK-DIO3 Genomic Region in Placental Mammals Mol. Biol. Evol., May 1, 2008; 25(5): 939 - 948. [Abstract] [Full Text] [PDF]

				C. D Stoddard, S. D. Gilbert, and R. T. Batey Ligand-dependent folding of the three-way junction in the purine riboswitch RNA, April 1, 2008; 14(4): 675 - 684. [Abstract] [Full Text] [PDF]

				T. Mourier, C. Carret, S. Kyes, Z. Christodoulou, P. P. Gardner, D. C. Jeffares, R. Pinches, B. Barrell, M. Berriman, S. Griffiths-Jones, et al. Genome-wide discovery and verification of novel structured RNAs in Plasmodium falciparum Genome Res., February 1, 2008; 18(2): 281 - 292. [Abstract] [Full Text] [PDF]

				J. Hertel, I. L. Hofacker, and P. F. Stadler SnoReport: computational identification of snoRNAs with unknown targets Bioinformatics, January 15, 2008; 24(2): 158 - 164. [Abstract] [Full Text] [PDF]

				G. Cochrane, R. Akhtar, P. Aldebert, N. Althorpe, A. Baldwin, K. Bates, S. Bhattacharyya, J. Bonfield, L. Bower, P. Browne, et al. Priorities for nucleotide trace, sequence and annotation data capture at the Ensembl Trace Archive and the EMBL Nucleotide Sequence Database Nucleic Acids Res., January 11, 2008; 36(suppl_1): D5 - D12. [Abstract] [Full Text] [PDF]

				Y. Zhou, C. Lu, Q.-J. Wu, Y. Wang, Z.-T. Sun, J.-C. Deng, and Y. Zhang GISSD: Group I Intron Sequence and Structure Database Nucleic Acids Res., January 11, 2008; 36(suppl_1): D31 - D37. [Abstract] [Full Text] [PDF]

				E. A. Bruford, M. J. Lush, M. W. Wright, T. P. Sneddon, S. Povey, and E. Birney The HGNC Database in 2008: a resource for the human genome Nucleic Acids Res., January 11, 2008; 36(suppl_1): D445 - D448. [Abstract] [Full Text] [PDF]

				S. Gama-Castro, V. Jimenez-Jacinto, M. Peralta-Gil, A. Santos-Zavaleta, M. I. Penaloza-Spinola, B. Contreras-Moreira, J. Segura-Salazar, L. Muniz-Rascado, I. Martinez-Flores, H. Salgado, et al. RegulonDB (version 6.0): gene regulation model of Escherichia coli K-12 beyond transcription, active (experimental) annotated promoters and Textpresso navigation Nucleic Acids Res., January 11, 2008; 36(suppl_1): D120 - D124. [Abstract] [Full Text] [PDF]

				S. Schwartz, J. Silva, D. Burstein, T. Pupko, E. Eyras, and G. Ast Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes Genome Res., January 1, 2008; 18(1): 88 - 103. [Abstract] [Full Text] [PDF]

				J. A. Collins, I. Irnov, S. Baker, and W. C. Winkler Mechanism of mRNA destabilization by the glmS ribozyme Genes & Dev., December 15, 2007; 21(24): 3356 - 3368. [Abstract] [Full Text] [PDF]

				S. Lindgreen, P. P. Gardner, and A. Krogh MASTR: multiple alignment and structure prediction of non-coding RNAs using simulated annealing Bioinformatics, December 15, 2007; 23(24): 3304 - 3311. [Abstract] [Full Text] [PDF]

				J. P. McCutcheon and N. A. Moran Parallel genomic evolution and metabolic interdependence in an ancient symbiosis PNAS, December 4, 2007; 104(49): 19392 - 19397. [Abstract] [Full Text] [PDF]

				G. Terai, T. Komori, K. Asai, and T. Kin miRRim: A novel system to find conserved miRNAs with high sensitivity and specificity RNA, December 1, 2007; 13(12): 2081 - 2090. [Abstract] [Full Text] [PDF]

				I. M. Meyer A practical guide to the art of RNA gene prediction Brief Bioinform, November 1, 2007; 8(6): 396 - 414. [Abstract] [Full Text] [PDF]

				A. Klevan, N. J. Tourasse, F. B. Stabell, A.-B. Kolsto, and O. A. Okstad Exploring the evolution of the Bacillus cereus group repeat element bcr1 by comparative genome analysis of closely related strains Microbiology, November 1, 2007; 153(11): 3894 - 3908. [Abstract] [Full Text] [PDF]

				E. S. Andersen, A. Lind-Thomsen, B. Knudsen, S. E. Kristensen, J. H. Havgaard, E. Torarinsson, N. Larsen, C. Zwieb, P. Sestoft, J. Kjems, et al. Semiautomated improvement of RNA alignments RNA, November 1, 2007; 13(11): 1850 - 1859. [Abstract] [Full Text] [PDF]

				A. Laederach Informatics challenges in structured RNA Brief Bioinform, September 1, 2007; 8(5): 294 - 303. [Abstract] [Full Text] [PDF]

				X. Xu, Y. Ji, and G. D. Stormo RNA Sampler: a new sampling based algorithm for common RNA secondary structure prediction and structural alignment Bioinformatics, August 1, 2007; 23(15): 1883 - 1891. [Abstract] [Full Text] [PDF]

				L. Kong, Y. Zhang, Z.-Q. Ye, X.-Q. Liu, S.-Q. Zhao, L. Wei, and G. Gao CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine Nucleic Acids Res., July 13, 2007; 35(suppl_2): W345 - W349. [Abstract] [Full Text] [PDF]

				C. Aksay, R. Salari, E. Karakoc, C. Alkan, and S. C. Sahinalp taveRNA: a web suite for RNA algorithms and applications Nucleic Acids Res., July 13, 2007; 35(suppl_2): W325 - W329. [Abstract] [Full Text] [PDF]

				M. Khaladkar, V. Bellofatto, J. T. L. Wang, B. Tian, and B. A. Shapiro RADAR: a web server for RNA data analysis and research Nucleic Acids Res., July 13, 2007; 35(suppl_2): W300 - W304. [Abstract] [Full Text] [PDF]

				J. Reeder, J. Reeder, and R. Giegerich Locomotif: from graphical motif description to RNA motif search Bioinformatics, July 1, 2007; 23(13): i392 - i400. [Abstract] [Full Text] [PDF]

				S. Washietl, J. S. Pedersen, J. O. Korbel, C. Stocsits, A. R. Gruber, J. Hackermuller, J. Hertel, M. Lindemeyer, K. Reiche, A. Tanzer, et al. Structured RNAs in the ENCODE selected regions of the human genome Genome Res., June 1, 2007; 17(6): 852 - 864. [Abstract] [Full Text] [PDF]

				C. A. Davis, M. P. S. Brown, and U. Singh Functional Characterization of Spliceosomal Introns and Identification of U2, U4, and U5 snRNAs in the Deep-Branching Eukaryote Entamoeba histolytica Eukaryot. Cell, June 1, 2007; 6(6): 940 - 948. [Abstract] [Full Text] [PDF]

				K. L. S. Ng and S. K. Mishra De novo SVM classification of precursor microRNAs from genomic pseudo hairpins using global and intrinsic folding measures Bioinformatics, June 1, 2007; 23(11): 1321 - 1330. [Abstract] [Full Text] [PDF]

				T. Zhao, G. Li, S. Mi, S. Li, G. J. Hannon, X.-J. Wang, and Y. Qi A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii Genes & Dev., May 15, 2007; 21(10): 1190 - 1203. [Abstract] [Full Text] [PDF]

This Article Abstract Print PDF (229K) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Commercial Re-use Guidelines for Open Access NAR Content Google Scholar Articles by Griffiths-Jones, S. Articles by Bateman, A. Search for Related Content PubMed PubMed Citation Articles by Griffiths-Jones, S. Articles by Bateman, A. Social Bookmarking          What's this?

Online ISSN 1362-4962 - Print ISSN 0305-1048

Copyright © 2009 Oxford University Press

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics