Hairpins in a Haystack: recognizing microRNA precursors in comparative genomics data

UNLABELLED Recently, genome-wide surveys for non-coding RNAs have provided evidence for tens of thousands of previously undescribed evolutionary conserved RNAs with distinctive secondary structures. The annotation of these putative ncRNAs, however, remains a difficult problem. Here we describe an SVM-based approach that, in conjunction with a non-stringent filter for consensus secondary structures, is capable of efficiently recognizing microRNA precursors in multiple sequence alignments. The software was applied to recent genome-wide RNAz surveys of mammals, urochordates, and nematodes. AVAILABILITY The program RNAmicro is available as source code and can be downloaded from http://www.bioinf.uni-leipzig/Software/RNAmicro.

[1]  Daniel H. Huson,et al.  Identification of plant microRNA homologs , 2006, Bioinform..

[2]  C. Kidner,et al.  The developmental role of microRNA in plants. , 2005, Current opinion in plant biology.

[3]  D. Haussler,et al.  Aligning multiple genomic sequences with the threaded blockset aligner. , 2004, Genome research.

[4]  Elena Rivas,et al.  Noncoding RNA gene detection using comparative sequence analysis , 2001, BMC Bioinformatics.

[5]  Michel J. Weber.  New human and mouse microRNA genes found by homology search , 2004, The FEBS journal.

[6]  C. Burge,et al.  Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification. , 2004, RNA.

[7]  Hanah Margalit,et al.  Clustering and conservation patterns of human microRNAs , 2005, Nucleic acids research.

[8]  P. Stadler,et al.  Secondary structure prediction for aligned RNA sequences. , 2002, Journal of molecular biology.

[9]  Walter Fontana,et al.  Fast folding and comparison of RNA secondary structures , 1994 .

[10]  S. Eddy,et al.  tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. , 1997, Nucleic acids research.

[11]  Daniel Gautheret,et al.  Profile-based detection of microRNA precursors in animal genomes , 2005, Bioinform..

[12]  C. Burge,et al.  The microRNAs of Caenorhabditis elegans. , 2003, Genes & development.

[13]  Lesley J. Collins,et al.  Searching for ncRNAs in eukaryotic genomes: Maximizing biological input with RNAmotif , 2004, J. Integr. Bioinform..

[14]  S. Cox,et al.  Evidence that miRNAs are different from other RNAs , 2006, Cellular and Molecular Life Sciences CMLS.

[15]  Michael Gribskov,et al.  Combining evidence using p-values: application to sequence homology searches , 1998, Bioinform..

[16]  Peter F Stadler,et al.  Fast and reliable prediction of noncoding RNAs , 2005, Proc. Natl. Acad. Sci. USA.

[17]  Christoph Flamm,et al.  The expansion of the metazoan microRNA repertoire , 2006, BMC Genomics.

[18]  Fei Li,et al.  MicroRNA identification based on sequence and structure alignment , 2005, Bioinform..

[19]  Sean R. Eddy,et al.  Rfam: annotating non-coding RNAs in complete genomes , 2004, Nucleic Acids Res..

[20]  D. Bartel,et al.  Antiquity of MicroRNAs and Their Targets in Land Plantsw⃞ , 2005, The Plant Cell Online.

[21]  Peter F. Stadler,et al.  Non-coding RNAs in Ciona intestinalis , 2005, ECCB/JBI.

[22]  R. Aharonov,et al.  Identification of hundreds of conserved and nonconserved human microRNAs , 2005, Nature Genetics.

[23]  D. Bartel,et al.  Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs , 2004, Nature Reviews Genetics.

[24]  J. Mattick.  RNA regulation: a new genetics? , 2004, Nature Reviews Genetics.

[25]  D. Haussler,et al.  Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. , 2005, Genome research.

[26]  C. Burge,et al.  Vertebrate MicroRNA Genes , 2003, Science.

[27]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

[28]  T. Tuschl,et al.  Identification of Tissue-Specific MicroRNAs from Mouse , 2002, Current Biology.

[29]  K. Lindblad-Toh,et al.  Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals , 2005, Nature.

[30]  Baohong Zhang,et al.  Identification and characterization of new plant microRNAs using EST analysis , 2005, Cell Research.

[31]  V. Ambros.  The functions of animal microRNAs , 2004, Nature.

[32]  P. Clote,et al.  Structural RNA has lower folding energy than random RNA of the same dinucleotide frequency. , 2005, RNA.

[33]  G. Rubin,et al.  Computational identification of Drosophila microRNA genes , 2003, Genome Biology.

[34]  Byoung-Tak Zhang,et al.  Human microRNA prediction through a probabilistic co-learning model of sequence and structure , 2005, Nucleic acids research.

[35]  Mihaela Zavolan,et al.  Identification of Clustered Micrornas Using an Ab Initio Prediction Method , 2022 .

[36]  D. O. Wijnands,et al.  Identification of plants , 1997 .

[37]  Yves Van de Peer,et al.  Evidence that microRNA precursors, unlike other non-coding RNAs, have lower folding free energies than random sequences , 2004, Bioinform..

[38]  B. Patterson,et al.  Letter to the editor. , 2018, Journal of professional nursing : official journal of the American Association of Colleges of Nursing.

[39]  David Haussler,et al.  Identification and Classification of Conserved RNA Secondary Structures in the Human Genome , 2006, PLoS Comput. Biol..

[40]  Tore Samuelsson,et al.  Identification and analysis of ribonuclease P and MRP RNA in a broad range of eukaryotes , 2005, Nucleic acids research.

[41]  Sam Griffiths-Jones,et al.  The microRNA Registry , 2004, Nucleic Acids Res..

[42]  Fei Li,et al.  Classification of real and pseudo microRNA precursors using local structure-sequence features and support vector machine , 2005, BMC Bioinformatics.

[43]  Peter F Stadler,et al.  Molecular evolution of a microRNA cluster. , 2004, Journal of molecular biology.

[44]  Shao-Yao Ying.  Current perspectives in microRNAs (miRNA) , 2008 .

[45]  P. Stadler,et al.  Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome , 2005, Nature Biotechnology.

[46]  G. Church,et al.  Computational and experimental identification of C. elegans microRNAs. , 2003, Molecular cell.