A Practical Guide to miRNA Target Prediction.

MicroRNAs (miRNAs) are small endogenous noncoding RNA molecules that posttranscriptionally regulate gene expression. Since their discovery, a huge number of miRNAs have been identified in a wide range of species. Through binding to the 3' UTR of mRNA, miRNA can block translation or stimulate degradation of the targeted mRNA, thus affecting nearly all biological processes. Prediction and identification of miRNA target genes is crucial toward understanding the biology of miRNAs. Currently, a number of sophisticated bioinformatics approaches are available to perform effective prediction of miRNA target sites. In this chapter, we present the major features that most algorithms take into account to efficiently predict miRNA target: seed match, free energy, conservation, target site accessibility, and contribution of multiple binding sites. We also give an overview of the frequently used bioinformatics tools for miRNA target prediction. Understanding the basis of these prediction methodologies may help users to better select the appropriate tools and analyze their output.

[1]  L. Pachter,et al.  Strategies and tools for whole-genome alignments. , 2002, Genome research.

[2]  Y. Suh,et al.  Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging , 2017, Mechanisms of Ageing and Development.

[3]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[4]  Yi-Hsuan Chen,et al.  miRNAMap 2.0: genomic maps of microRNAs in metazoan genomes , 2007, Nucleic Acids Res..

[5]  M. Waterman,et al.  A new algorithm for best subsequence alignments with application to tRNA-rRNA comparisons. , 1987, Journal of molecular biology.

[6]  Martin Reczko,et al.  DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows , 2013, Nucleic Acids Res..

[7]  Hsien-Da Huang,et al.  miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes , 2005, Nucleic Acids Res..

[8]  Jeffrey A. Thompson,et al.  Common features of microRNA target prediction tools , 2014, Front. Genet..

[9]  H. Ruohola-Baker,et al.  Stem cell division is regulated by the microRNA pathway , 2005, Nature.

[10]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[11]  Annick Harel-Bellan,et al.  The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation , 2006, Nature Cell Biology.

[12]  Chao Wu,et al.  ToppMiR: ranking microRNAs and their mRNA targets based on biological functions and context , 2014, Nucleic Acids Res..

[13]  Yuanji Zhang,et al.  miRU: an automated plant miRNA target prediction server , 2005, Nucleic Acids Res..

[14]  Matthias Blum,et al.  miRmap web: comprehensive microRNA target prediction online , 2013, Nucleic Acids Res..

[15]  W. Ritchie,et al.  Predicting microRNA targets and functions: traps for the unwary , 2009, Nature Methods.

[16]  Panayiotis V. Benos,et al.  ComiR: combinatorial microRNA target prediction tool , 2013, Nucleic Acids Res..

[17]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[18]  R. Giegerich,et al.  Fast and effective prediction of microRNA/target duplexes. , 2004, RNA.

[19]  Yong Zhao,et al.  Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis , 2005, Nature.

[20]  E. Lai.  Predicting and validating microRNA targets , 2004, Genome Biology.

[21]  Anton J. Enright,et al.  Human MicroRNA Targets , 2004, PLoS biology.

[22]  Y. Li,et al.  Incorporating structure to predict microRNA targets. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Anjali J. Koppal,et al.  Supplementary data: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites , 2010 .

[24]  Ivo Grosse,et al.  Functional microRNA targets in protein coding sequences , 2012, Bioinform..

[25]  Norbert Gretz,et al.  miRWalk - Database: Prediction of possible miRNA binding sites by "walking" the genes of three genomes , 2011, J. Biomed. Informatics.

[26]  M. Byrom,et al.  Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis , 2005, Nucleic acids research.

[27]  Michael Kertesz,et al.  The role of site accessibility in microRNA target recognition , 2007, Nature Genetics.

[28]  Xiaowei Wang.  miRDB: a microRNA target prediction and functional annotation database with a wiki interface. , 2008, RNA.

[29]  W. Ritchie,et al.  MicroRNA target prediction and validation. , 2013, Advances in experimental medicine and biology.

[30]  W. Cho.  MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. , 2010, The international journal of biochemistry & cell biology.

[31]  Jirí Vanícek,et al.  Efficient use of accessibility in microRNA target prediction , 2010, Nucleic Acids Res..

[32]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[33]  C. Bracken,et al.  Experimental strategies for microRNA target identification , 2011, Nucleic acids research.

[34]  G. Santulli,et al.  Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis. , 2015, Advances in experimental medicine and biology.

[35]  Nicholas L. Bray,et al.  AVID: A global alignment program. , 2003, Genome research.

[36]  William A. Rennie,et al.  CLIP-based prediction of mammalian microRNA binding sites , 2013, Nucleic acids research.

[37]  Xiaowei Wang,et al.  miRDB: an online resource for microRNA target prediction and functional annotations , 2014, Nucleic Acids Res..

[38]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[39]  Charles E. Vejnar,et al.  miRmap: Comprehensive prediction of microRNA target repression strength , 2012, Nucleic acids research.

[40]  Dang D. Long,et al.  Potent effect of target structure on microRNA function , 2007, Nature Structural &Molecular Biology.

[41]  Doron Betel,et al.  The microRNA.org resource: targets and expression , 2007, Nucleic Acids Res..

[42]  Ana Kozomara,et al.  miRBase: annotating high confidence microRNAs using deep sequencing data , 2013, Nucleic Acids Res..

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

[44]  Yvonne Tay,et al.  A Pattern-Based Method for the Identification of MicroRNA Binding Sites and Their Corresponding Heteroduplexes , 2006, Cell.

[45]  Masaru Tomita,et al.  Computational analysis of microRNA targets in Caenorhabditis elegans. , 2006, Gene.

[46]  Jun Lu,et al.  STarMir: a web server for prediction of microRNA binding sites , 2014, Nucleic Acids Res..

[47]  Susumu Goto,et al.  KEGG for integration and interpretation of large-scale molecular data sets , 2011, Nucleic Acids Res..

[48]  Anton J. Enright,et al.  MicroRNA targets in Drosophila , 2003, Genome Biology.

[49]  Colin N. Dewey,et al.  A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans , 2006, Current Biology.

[50]  Michal Linial,et al.  MiRror: a combinatorial analysis web tool for ensembles of microRNAs and their targets , 2010, Bioinform..

[51]  Jan Krüger,et al.  RNAhybrid: microRNA target prediction easy, fast and flexible , 2006, Nucleic Acids Res..

[52]  I. Jurisica,et al.  NAViGaTing the Micronome – Using Multiple MicroRNA Prediction Databases to Identify Signalling Pathway-Associated MicroRNAs , 2011, PloS one.

[53]  D. Karolchik,et al.  The UCSC Genome Browser database: 2016 update , 2015, bioRxiv.

[54]  Most Mauluda Akhtar,et al.  Bioinformatic tools for microRNA dissection , 2015, Nucleic acids research.

[55]  Most Mauluda Akhtar,et al.  Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis , 2016, Oncotarget.

[56]  Xia Li,et al.  mirTarPri: Improved Prioritization of MicroRNA Targets through Incorporation of Functional Genomics Data , 2013, PloS one.

[57]  Isidore Rigoutsos,et al.  Interactive exploration of RNA22 microRNA target predictions , 2012, Bioinform..

[58]  Hsien-Da Huang,et al.  miRTar: an integrated system for identifying miRNA-target interactions in human , 2011, BMC Bioinformatics.

[59]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[60]  Nectarios Koziris,et al.  DIANA-microT Web server upgrade supports Fly and Worm miRNA target prediction and bibliographic miRNA to disease association , 2011, Nucleic Acids Res..

[61]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[62]  P. Schuster,et al.  Complete suboptimal folding of RNA and the stability of secondary structures. , 1999, Biopolymers.

[63]  R. Gregory,et al.  Many roads to maturity: microRNA biogenesis pathways and their regulation , 2009, Nature Cell Biology.

[64]  Michal Linial,et al.  miRror-Suite: decoding coordinated regulation by microRNAs , 2014, Database J. Biol. Databases Curation.

[65]  C. Burge,et al.  The Widespread Impact of Mammalian MicroRNAs on mRNA Repression and Evolution , 2005, Science.

[66]  D. Bartel,et al.  Predicting effective microRNA target sites in mammalian mRNAs , 2015, eLife.

[67]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[68]  Nectarios Koziris,et al.  DIANA-microT web server: elucidating microRNA functions through target prediction , 2009, Nucleic Acids Res..