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PMID: 19295136 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Current tools for the identification of miRNA genes and their targets.

Nucleic acids research ·Vol. 37 ·No. 8 ·2009-05-00 ·Pages 2419-33

Mendes ND, Freitas AT, Sagot MF

Abstract

The discovery of microRNAs (miRNAs), almost 10 years ago, changed dramatically our perspective on eukaryotic gene expression regulation. However, the broad and important functions of these regulators are only now becoming apparent. The expansion of our catalogue of miRNA genes and the identification of the genes they regulate owe much to the development of sophisticated computational tools that have helped either to focus or interpret experimental assays. In this article, we review the methods for miRNA gene finding and target identification that have been proposed in the last few years. We identify some problems that current approaches have not yet been able to overcome and we offer some perspectives on the next generation of computational methods.

MeSH Terms
Animals Computational Biology/methods Genes MicroRNAs/biosynthesis,genetics,metabolism RNA Interference RNA, Messenger/chemistry,metabolism
Chemicals
MicroRNAs RNA, Messenger
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mendes N D
Equipe BAOBAB, Laboratoire de Biométrie et Biologie Evolutive (UMR 5558), CNRS, Univ. Lyon 1, 43 bd du 11 nov 1918, 69622, Villeurbanne Cedex, France. ndm@kdbio.inesc-id.pt
Freitas A T
Sagot M-F
References (134)
134 references, click to expand
  1. Discovering microRNAs from deep sequencing data using miRDeep.
    Nat Biotechnol. 2008 Apr;26(4):407-15 PMID: 18392026
  2. MicroTar: predicting microRNA targets from RNA duplexes.
    BMC Bioinformatics. 2006 Dec 18;7 Suppl 5:S20 PMID: 17254305
  3. mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein-enriched transcripts.
    Nat Methods. 2008 Sep;5(9):813-9 PMID: 19160516
  4. RNA polymerase III transcribes human microRNAs.
    Nat Struct Mol Biol. 2006 Dec;13(12):1097-101 PMID: 17099701
  5. Combinatorial microRNA target predictions.
    Nat Genet. 2005 May;37(5):495-500 PMID: 15806104
  6. Fast and effective prediction of microRNA/target duplexes.
    RNA. 2004 Oct;10(10):1507-17 PMID: 15383676
  7. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.
    Nature. 2005 Feb 17;433(7027):769-73 PMID: 15685193
  8. Evidence that miRNAs are different from other RNAs.
    Cell Mol Life Sci. 2006 Jan;63(2):246-54 PMID: 16395542
  9. Antisense transcripts in the human genome.
    Trends Genet. 2002 Feb;18(2):63-5 PMID: 11818131
  10. A microRNA as a translational repressor of APETALA2 in Arabidopsis flower development.
    Science. 2004 Mar 26;303(5666):2022-5 PMID: 12893888
  11. MicroRNA maturation: stepwise processing and subcellular localization.
    EMBO J. 2002 Sep 2;21(17):4663-70 PMID: 12198168
  12. The microRNAs of Caenorhabditis elegans.
    Genes Dev. 2003 Apr 15;17(8):991-1008 PMID: 12672692
  13. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms.
    Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9779-84 PMID: 12902540
  14. Identification of plant microRNA homologs.
    Bioinformatics. 2006 Feb 1;22(3):359-60 PMID: 16317073
  15. MiPred: classification of real and pseudo microRNA precursors using random forest prediction model with combined features.
    Nucleic Acids Res. 2007 Jul;35(Web Server issue):W339-44 PMID: 17553836
  16. Identification of novel and candidate miRNAs in rice by high throughput sequencing.
    BMC Plant Biol. 2008 Feb 29;8:25 PMID: 18312648
  17. Human MicroRNA targets.
    PLoS Biol. 2004 Nov;2(11):e363 PMID: 15502875
  18. An extensive class of small RNAs in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):862-4 PMID: 11679672
  19. An approach for the identification of microRNA with an application to Anopheles gambiae.
    Acta Biochim Pol. 2006;53(2):303-9 PMID: 16770443
  20. Identification of virus-encoded microRNAs.
    Science. 2004 Apr 30;304(5671):734-6 PMID: 15118162
  21. RNA editing of a miRNA precursor.
    RNA. 2004 Aug;10(8):1174-7 PMID: 15272117
  22. miTarget: microRNA target gene prediction using a support vector machine.
    BMC Bioinformatics. 2006 Sep 18;7:411 PMID: 16978421
  23. Human microRNA prediction through a probabilistic co-learning model of sequence and structure.
    Nucleic Acids Res. 2005 Jun 24;33(11):3570-81 PMID: 15987789
  24. A combined computational-experimental approach predicts human microRNA targets.
    Genes Dev. 2004 May 15;18(10):1165-78 PMID: 15131085
  25. Hairpins in a Haystack: recognizing microRNA precursors in comparative genomics data.
    Bioinformatics. 2006 Jul 15;22(14):e197-202 PMID: 16873472
  26. Intronic microRNA precursors that bypass Drosha processing.
    Nature. 2007 Jul 5;448(7149):83-6 PMID: 17589500
  27. MicroRNAs and other tiny endogenous RNAs in C. elegans.
    Curr Biol. 2003 May 13;13(10):807-18 PMID: 12747828
  28. Identification of microRNAs of the herpesvirus family.
    Nat Methods. 2005 Apr;2(4):269-76 PMID: 15782219
  29. siRNA and miRNA: an insight into RISCs.
    Trends Biochem Sci. 2005 Feb;30(2):106-14 PMID: 15691656
  30. Computational and experimental identification of C. elegans microRNAs.
    Mol Cell. 2003 May;11(5):1253-63 PMID: 12769849
  31. Human microRNAs target a functionally distinct population of genes with AT-rich 3' UTRs.
    Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15557-62 PMID: 16230613
  32. MicroRNA-373 induces expression of genes with complementary promoter sequences.
    Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1608-13 PMID: 18227514
  33. Mammalian microRNAs derived from genomic repeats.
    Trends Genet. 2005 Jun;21(6):322-6 PMID: 15922829
  34. Processing of intronic microRNAs.
    EMBO J. 2007 Feb 7;26(3):775-83 PMID: 17255951
  35. Structural requirements for pre-microRNA binding and nuclear export by Exportin 5.
    Nucleic Acids Res. 2004 Sep 08;32(16):4776-85 PMID: 15356295
  36. RNA editing of human microRNAs.
    Genome Biol. 2006;7(4):R27 PMID: 16594986
  37. Reliable prediction of Drosha processing sites improves microRNA gene prediction.
    Bioinformatics. 2007 Jan 15;23(2):142-9 PMID: 17105718
  38. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex.
    Cell. 2006 Jun 2;125(5):887-901 PMID: 16751099
  39. Prediction of both conserved and nonconserved microRNA targets in animals.
    Bioinformatics. 2008 Feb 1;24(3):325-32 PMID: 18048393
  40. MicroRNA-directed cleavage of HOXB8 mRNA.
    Science. 2004 Apr 23;304(5670):594-6 PMID: 15105502
  41. microRNAs: tiny regulators with great potential.
    Cell. 2001 Dec 28;107(7):823-6 PMID: 11779458
  42. Computational identification of plant microRNAs and their targets, including a stress-induced miRNA.
    Mol Cell. 2004 Jun 18;14(6):787-99 PMID: 15200956
  43. MicroRNA identification based on sequence and structure alignment.
    Bioinformatics. 2005 Sep 15;21(18):3610-4 PMID: 15994192
  44. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.
    Nature. 2000 Nov 2;408(6808):86-9 PMID: 11081512
  45. microRNA target predictions in animals.
    Nat Genet. 2006 Jun;38 Suppl:S8-13 PMID: 16736023
  46. Identification of hundreds of conserved and nonconserved human microRNAs.
    Nat Genet. 2005 Jul;37(7):766-70 PMID: 15965474
  47. Inferring microRNA activities by combining gene expression with microRNA target prediction.
    PLoS One. 2008 Apr 23;3(4):e1989 PMID: 18431476
  48. Computational identification of Drosophila microRNA genes.
    Genome Biol. 2003;4(7):R42 PMID: 12844358
  49. Novel and stress-regulated microRNAs and other small RNAs from Arabidopsis.
    Plant Cell. 2004 Aug;16(8):2001-19 PMID: 15258262
  50. Regulation of flowering time and floral organ identity by a MicroRNA and its APETALA2-like target genes.
    Plant Cell. 2003 Nov;15(11):2730-41 PMID: 14555699
  51. Computational and transcriptional evidence for microRNAs in the honey bee genome.
    Genome Biol. 2007;8(6):R97 PMID: 17543122
  52. The role of site accessibility in microRNA target recognition.
    Nat Genet. 2007 Oct;39(10):1278-84 PMID: 17893677
  53. Structural features of microRNA (miRNA) precursors and their relevance to miRNA biogenesis and small interfering RNA/short hairpin RNA design.
    J Biol Chem. 2004 Oct 1;279(40):42230-9 PMID: 15292246
  54. Clustering and conservation patterns of human microRNAs.
    Nucleic Acids Res. 2005 May 12;33(8):2697-706 PMID: 15891114
  55. Incorporating structure to predict microRNA targets.
    Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4006-9 PMID: 15738385
  56. Specificity of microRNA target selection in translational repression.
    Genes Dev. 2004 Mar 1;18(5):504-11 PMID: 15014042
  57. Micro RNAs are complementary to 3' UTR sequence motifs that mediate negative post-transcriptional regulation.
    Nat Genet. 2002 Apr;30(4):363-4 PMID: 11896390
  58. MicroRNA function: multiple mechanisms for a tiny RNA?
    RNA. 2005 Dec;11(12):1753-61 PMID: 16314451
  59. Combining multi-species genomic data for microRNA identification using a Naive Bayes classifier.
    Bioinformatics. 2006 Jun 1;22(11):1325-34 PMID: 16543277
  60. Identification of mammalian microRNA host genes and transcription units.
    Genome Res. 2004 Oct;14(10A):1902-10 PMID: 15364901
  61. Profile-based detection of microRNA precursors in animal genomes.
    Bioinformatics. 2005 Apr 1;21(7):841-5 PMID: 15509608
  62. Substrate requirements for let-7 function in the developing zebrafish embryo.
    Nucleic Acids Res. 2004 Dec 07;32(21):6284-91 PMID: 15585662
  63. Comparing sequence and expression for predicting microRNA targets using GenMiR3.
    Pac Symp Biocomput. 2008;:52-63 PMID: 18229676
  64. Computational identification of novel family members of microRNA genes in Arabidopsis thaliana and Oryza sativa.
    Acta Biochim Biophys Sin (Shanghai). 2005 Feb;37(2):75-87 PMID: 15685364
  65. Computational identification of microRNA targets.
    Dev Biol. 2004 Mar 15;267(2):529-35 PMID: 15013811
  66. Detection of 91 potential conserved plant microRNAs in Arabidopsis thaliana and Oryza sativa identifies important target genes.
    Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11511-6 PMID: 15272084
  67. Ab initio identification of human microRNAs based on structure motifs.
    BMC Bioinformatics. 2007 Dec 18;8:478 PMID: 18088431
  68. Patterns of flanking sequence conservation and a characteristic upstream motif for microRNA gene identification.
    RNA. 2004 Sep;10(9):1309-22 PMID: 15317971
  69. Prediction and identification of Arabidopsis thaliana microRNAs and their mRNA targets.
    Genome Biol. 2004;5(9):R65 PMID: 15345049
  70. Conservation and divergence of plant microRNA genes.
    Plant J. 2006 Apr;46(2):243-59 PMID: 16623887
  71. Identification of novel Drosophila melanogaster microRNAs.
    PLoS One. 2007 Nov 28;2(11):e1265 PMID: 18043761
  72. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes.
    RNA. 2005 Mar;11(3):241-7 PMID: 15701730
  73. Mammalian microRNA prediction through a support vector machine model of sequence and structure.
    PLoS One. 2007 Sep 26;2(9):e946 PMID: 17895987
  74. RNA stem-loops: to be or not to be cleaved by RNAse III.
    RNA. 2007 Apr;13(4):457-62 PMID: 17299129
  75. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR.
    Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9667-72 PMID: 17535905
  76. Architecture of a validated microRNA::target interaction.
    Chem Biol. 2004 Dec;11(12):1619-23 PMID: 15610845
  77. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.
    Science. 2001 Oct 26;294(5543):858-62 PMID: 11679671
  78. Silence from within: endogenous siRNAs and miRNAs.
    Cell. 2005 Jul 15;122(1):9-12 PMID: 16009127
  79. Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs.
    Genome Res. 2007 Dec;17(12):1850-64 PMID: 17989254
  80. MicroRNAs in plants.
    Genes Dev. 2002 Jul 1;16(13):1616-26 PMID: 12101121
  81. MicroRNAs: at the root of plant development?
    Plant Physiol. 2003 Jun;132(2):709-17 PMID: 12805599
  82. Nuclear export of microRNA precursors.
    Science. 2004 Jan 2;303(5654):95-8 PMID: 14631048
  83. Intronic microRNAs.
    Biochem Biophys Res Commun. 2005 Jan 21;326(3):515-20 PMID: 15596130
  84. A-to-I editing challenger or ally to the microRNA process.
    Biochimie. 2007 Oct;89(10):1171-6 PMID: 17628290
  85. Evidence that microRNA precursors, unlike other non-coding RNAs, have lower folding free energies than random sequences.
    Bioinformatics. 2004 Nov 22;20(17):2911-7 PMID: 15217813
  86. Nuclear processing and export of microRNAs in Arabidopsis.
    Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3691-6 PMID: 15738428
  87. Prediction of microRNA targets.
    Drug Discov Today. 2007 Jun;12(11-12):452-8 PMID: 17532529
  88. Direct RNA motif definition and identification from multiple sequence alignments using secondary structure profiles.
    J Mol Biol. 2001 Nov 9;313(5):1003-11 PMID: 11700055
  89. A mammalian microRNA expression atlas based on small RNA library sequencing.
    Cell. 2007 Jun 29;129(7):1401-14 PMID: 17604727
  90. Inferring noncoding RNA families and classes by means of genome-scale structure-based clustering.
    PLoS Comput Biol. 2007 Apr 13;3(4):e65 PMID: 17432929
  91. MicroRNA genes are transcribed by RNA polymerase II.
    EMBO J. 2004 Oct 13;23(20):4051-60 PMID: 15372072
  92. Asymmetry of intronic pre-miRNA structures in functional RISC assembly.
    Gene. 2005 Aug 15;356:32-8 PMID: 16005165
  93. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.
    Cell. 2005 Jan 14;120(1):15-20 PMID: 15652477
  94. Computational prediction and experimental validation of Ciona intestinalis microRNA genes.
    BMC Genomics. 2007 Nov 29;8:445 PMID: 18047675
  95. Principles of microRNA-target recognition.
    PLoS Biol. 2005 Mar;3(3):e85 PMID: 15723116
  96. The nuclear RNase III Drosha initiates microRNA processing.
    Nature. 2003 Sep 25;425(6956):415-9 PMID: 14508493
  97. Prediction of plant microRNA targets.
    Cell. 2002 Aug 23;110(4):513-20 PMID: 12202040
  98. Prediction of mammalian microRNA targets.
    Cell. 2003 Dec 26;115(7):787-98 PMID: 14697198
  99. Direct evolution of genetic robustness in microRNA.
    Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6593-8 PMID: 16608911
  100. Functional siRNAs and miRNAs exhibit strand bias.
    Cell. 2003 Oct 17;115(2):209-16 PMID: 14567918
  101. Structure of the guide-strand-containing argonaute silencing complex.
    Nature. 2008 Nov 13;456(7219):209-13 PMID: 18754009
  102. Computational prediction of miRNAs in Arabidopsis thaliana.
    Genome Res. 2005 Jan;15(1):78-91 PMID: 15632092
  103. Vertebrate microRNA genes.
    Science. 2003 Mar 7;299(5612):1540 PMID: 12624257
  104. Switching from repression to activation: microRNAs can up-regulate translation.
    Science. 2007 Dec 21;318(5858):1931-4 PMID: 18048652
  105. Weighted sequence motifs as an improved seeding step in microRNA target prediction algorithms.
    RNA. 2005 Jul;11(7):995-1003 PMID: 15928346
  106. Revealing posttranscriptional regulatory elements through network-level conservation.
    PLoS Comput Biol. 2005 Dec;1(7):e69 PMID: 16355253
  107. Classification of real and pseudo microRNA precursors using local structure-sequence features and support vector machine.
    BMC Bioinformatics. 2005 Dec 29;6:310 PMID: 16381612
  108. New human and mouse microRNA genes found by homology search.
    FEBS J. 2005 Jan;272(1):59-73 PMID: 15634332
  109. Asymmetry in the assembly of the RNAi enzyme complex.
    Cell. 2003 Oct 17;115(2):199-208 PMID: 14567917
  110. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs.
    RNA. 2004 Dec;10(12):1957-66 PMID: 15525708
  111. MiRFinder: an improved approach and software implementation for genome-wide fast microRNA precursor scans.
    BMC Bioinformatics. 2007 Sep 17;8:341 PMID: 17868480
  112. Phylogenetic shadowing and computational identification of human microRNA genes.
    Cell. 2005 Jan 14;120(1):21-4 PMID: 15652478
  113. Computational RNomics of drosophilids.
    BMC Genomics. 2007 Nov 08;8:406 PMID: 17996037
  114. Prediction and verification of microRNA targets by MovingTargets, a highly adaptable prediction method.
    BMC Genomics. 2005 Jun 08;6:88 PMID: 15943864
  115. Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution.
    Cell. 2005 Dec 16;123(6):1133-46 PMID: 16337999
  116. Transcription and processing of human microRNA precursors.
    Mol Cell. 2004 Dec 22;16(6):861-5 PMID: 15610730
  117. Single processing center models for human Dicer and bacterial RNase III.
    Cell. 2004 Jul 9;118(1):57-68 PMID: 15242644
  118. A uniform system for microRNA annotation.
    RNA. 2003 Mar;9(3):277-9 PMID: 12592000
  119. MicroRNAs: genomics, biogenesis, mechanism, and function.
    Cell. 2004 Jan 23;116(2):281-97 PMID: 14744438
  120. Towards a complete description of the microRNA complement of animal genomes.
    Genome Biol. 2003;4(9):228 PMID: 12952528
  121. The 3' untranslated region of messenger RNA: A molecular 'hotspot' for pathology?
    Nat Med. 2000 Jun;6(6):637-41 PMID: 10835679
  122. Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals.
    Nature. 2005 Mar 17;434(7031):338-45 PMID: 15735639
  123. miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii.
    Nature. 2007 Jun 28;447(7148):1126-9 PMID: 17538623
  124. microRNAs: runts of the genome assert themselves.
    Curr Biol. 2003 Dec 2;13(23):R925-36 PMID: 14654021
  125. Identification of Drosophila MicroRNA targets.
    PLoS Biol. 2003 Dec;1(3):E60 PMID: 14691535
  126. De novo SVM classification of precursor microRNAs from genomic pseudo hairpins using global and intrinsic folding measures.
    Bioinformatics. 2007 Jun 1;23(11):1321-30 PMID: 17267435
  127. MicroRNA targets in Drosophila.
    Genome Biol. 2003;5(1):R1 PMID: 14709173
  128. Identification of clustered microRNAs using an ab initio prediction method.
    BMC Bioinformatics. 2005 Nov 07;6:267 PMID: 16274478
  129. Target mimics modulate miRNAs.
    Nat Genet. 2007 Aug;39(8):935-6 PMID: 17660806
  130. Inference of miRNA targets using evolutionary conservation and pathway analysis.
    BMC Bioinformatics. 2007 Mar 01;8:69 PMID: 17331257
  131. MicroRNA sequence motifs reveal asymmetry between the stem arms.
    Comput Biol Chem. 2006 Aug;30(4):249-54 PMID: 16798093
  132. Plant and animal microRNAs: similarities and differences.
    Funct Integr Genomics. 2005 Jul;5(3):129-35 PMID: 15875226
  133. Computational evidence for hundreds of non-conserved plant microRNAs.
    BMC Genomics. 2005 Sep 13;6:119 PMID: 16159385
  134. A microRNA in a multiple-turnover RNAi enzyme complex.
    Science. 2002 Sep 20;297(5589):2056-60 PMID: 12154197
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkp145
Email
ndm@kdbio.inesc-id.pt
Published
2009-05-00
Epub
2009-00-18
Pages
2419-33
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2677885
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkp145 PMC Full Text View journal details
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