Computational approaches for microRNA studies: a review

MicroRNAs (miRNAs) are one class of tiny, endogenous RNAs that can regulate messenger RNA (mRNA) expression by targeting homologous sequences in mRNAs. Their aberrant expressions have been observed in many cancers and several miRNAs have been convincingly shown to play important roles in carcinogenesis. Since the discovery of this small regulator, computational methods have been indispensable tools in miRNA gene finding and functional studies. In this review we first briefly outline the biological findings of miRNA genes, such as genomic feature, biogenesis, gene structure, and functional mechanism. We then discuss in detail the three main aspects of miRNA computational studies: miRNA gene finding, miRNA target prediction, and regulation of miRNA genes. Finally, we provide perspectives on some emerging issues, including combinatorial regulation by miRNAs and functional binding sites beyond the 3′-untranslated region (3′UTR) of target mRNAs. Available online resources for miRNA computational studies are also provided.

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

[2]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[3]  S. Shen-Orr,et al.  Network motifs: simple building blocks of complex networks. , 2002, Science.

[4]  V. Kim,et al.  MicroRNA maturation: stepwise processing and subcellular localization , 2002, The EMBO journal.

[5]  Anton J. Enright,et al.  MicroRNA Targets in Drosophila , 2003, Genome Biology.

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

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

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

[9]  A. Hatzigeorgiou,et al.  A combined computational-experimental approach predicts human microRNA targets. , 2004, Genes & development.

[10]  Sanghyuk Lee,et al.  MicroRNA genes are transcribed by RNA polymerase II , 2004, The EMBO journal.

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

[12]  B. Cullen,et al.  Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. , 2004, RNA.

[13]  Anton J. Enright,et al.  Identification of Virus-Encoded MicroRNAs , 2004, Science.

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

[15]  Kristin C. Gunsalus,et al.  microRNA Target Predictions across Seven Drosophila Species and Comparison to Mammalian Targets , 2005, PLoS Comput. Biol..

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

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

[18]  Byoung-Tak Zhang,et al.  miTarget: microRNA target gene prediction using a support vector machine , 2006, BMC Bioinformatics.

[19]  D. Ganem,et al.  MicroRNAs and viral infection. , 2005, Molecular cell.

[20]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[21]  Vesselin Baev,et al.  MicroInspector: a web tool for detection of miRNA binding sites in an RNA sequence , 2005, Nucleic Acids Res..

[22]  D. Bartel,et al.  Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. , 2005, RNA.

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

[24]  C. Sander,et al.  Identification of microRNAs of the herpesvirus family , 2005, Nature Methods.

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

[26]  Anton J. Enright,et al.  Materials and Methods Figs. S1 to S4 Tables S1 to S5 References and Notes Micrornas Regulate Brain Morphogenesis in Zebrafish , 2022 .

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

[28]  Ola Snøve,et al.  Weighted sequence motifs as an improved seeding step in microRNA target prediction algorithms. , 2005, RNA.

[29]  V. Kim.  MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

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

[31]  B. Davidson,et al.  RNA polymerase III transcribes human microRNAs , 2006, Nature Structural &Molecular Biology.

[32]  Peter F. Stadler,et al.  Hairpins in a Haystack: recognizing microRNA precursors in comparative genomics data , 2006, ISMB.

[33]  Guanglin Li,et al.  Prediction and Identification of Herpes Simplex Virus 1-Encoded MicroRNAs , 2006, Journal of Virology.

[34]  Anton J. Enright,et al.  Zebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAs , 2006, Science.

[35]  A. Hatzigeorgiou,et al.  A guide through present computational approaches for the identification of mammalian microRNA targets , 2006, Nature Methods.

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

[37]  Louise C. Showe,et al.  Bioinformatics Original Paper Combining Multi-species Genomic Data for Microrna Identification Using a Naı¨ve Bayes Classifier , 2022 .

[38]  Adam Grundhoff,et al.  A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. , 2006, RNA.

[39]  Byoung-Tak Zhang,et al.  ProMiR II: a web server for the probabilistic prediction of clustered, nonclustered, conserved and nonconserved microRNAs , 2006, Nucleic Acids Res..

[40]  E. Furth,et al.  Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster , 2006, Nature Genetics.

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

[42]  Martti T. Tammi,et al.  MicroTar: predicting microRNA targets from RNA duplexes , 2006, BMC Bioinformatics.

[43]  Eugene Berezikov,et al.  Mammalian mirtron genes. , 2007, Molecular cell.

[44]  Bin Fan,et al.  MiRFinder: an improved approach and software implementation for genome-wide fast microRNA precursor scans , 2007, BMC Bioinformatics.

[45]  Hsien-Da Huang,et al.  ViTa: prediction of host microRNAs targets on viruses , 2006, Nucleic Acids Res..

[46]  Anton J. Enright,et al.  Genomic analysis of human microRNA transcripts , 2007, Proceedings of the National Academy of Sciences.

[47]  D. Bartel,et al.  Intronic microRNA precursors that bypass Drosha processing , 2007, Nature.

[48]  E. Lai,et al.  The Mirtron Pathway Generates microRNA-Class Regulatory RNAs in Drosophila , 2007, Cell.

[49]  Santosh K. Mishra,et al.  De novo SVM classification of precursor microRNAs from genomic pseudo hairpins using global and intrinsic folding measures , 2007, Bioinform..

[50]  Peng Jiang,et al.  MiPred: classification of real and pseudo microRNA precursors using random forest prediction model with combined features , 2007, Nucleic Acids Res..

[51]  Weixiong Zhang,et al.  Characterization and Identification of MicroRNA Core Promoters in Four Model Species , 2007, PLoS Comput. Biol..

[52]  Louise C. Showe,et al.  Naïve Bayes for microRNA target predictions - machine learning for microRNA targets , 2007, Bioinform..

[53]  J. Steitz,et al.  Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR , 2007, Proceedings of the National Academy of Sciences.

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

[55]  E. Wentzel,et al.  A Hexanucleotide Element Directs MicroRNA Nuclear Import , 2007, Science.

[56]  Ola R. Snøve,et al.  Reliable prediction of Drosha processing sites improves microRNA gene prediction. , 2007, Bioinformatics.

[57]  Anton J. Enright,et al.  Prediction of microRNA targets. , 2007, Drug discovery today.

[58]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[59]  Jan Gorodkin,et al.  Principles and limitations of computational microRNA gene and target finding. , 2007, DNA and cell biology.

[60]  Zhihua Li,et al.  Regulatory Circuit of Human MicroRNA Biogenesis , 2007, PLoS Comput. Biol..

[61]  Carlo M. Croce,et al.  MicroRNAs 17-5p–20a–106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation , 2007, Nature Cell Biology.

[62]  Molly Megraw,et al.  miRGen: a database for the study of animal microRNA genomic organization and function , 2006, Nucleic Acids Res..

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

[64]  J. Yates,et al.  Systematic identification of C. elegans miRISC proteins, miRNAs, and mRNA targets by their interactions with GW182 proteins AIN-1 and AIN-2. , 2007, Molecular cell.

[65]  B. Frey,et al.  Using expression profiling data to identify human microRNA targets , 2007, Nature Methods.

[66]  George Easow,et al.  Isolation of microRNA targets by miRNP immunopurification. , 2007, RNA.

[67]  Wen-Hsiung Li,et al.  Prediction of human miRNAs using tissue-selective motifs in 3′ UTRs , 2008, Proceedings of the National Academy of Sciences.

[68]  P. Sætrom,et al.  MicroRNA-directed transcriptional gene silencing in mammalian cells , 2008, Proceedings of the National Academy of Sciences.

[69]  Chiwai Wong,et al.  A computational screen for mouse signaling pathways targeted by microRNA clusters. , 2008, RNA.

[70]  Paulo P. Amaral,et al.  The Eukaryotic Genome as an RNA Machine , 2008, Science.

[71]  Wen-chang Lin,et al.  Vir-Mir db: prediction of viral microRNA candidate hairpins , 2007, Nucleic Acids Res..

[72]  Anton J. Enright,et al.  Detecting microRNA binding and siRNA off-target effects from expression data , 2008, Nature Methods.

[73]  N. Rajewsky,et al.  Discovering microRNAs from deep sequencing data using miRDeep , 2008, Nature Biotechnology.

[74]  Megan F. Cole,et al.  Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells , 2008, Cell.

[75]  Jun S. Song,et al.  Chromatin structure analyses identify miRNA promoters , 2008 .

[76]  G. J. Hannon,et al.  Analysis of Large-Scale Sequencing of Small RNAs , 2007, Pacific Symposium on Biocomputing.

[77]  Lynn Doucette-Stamm,et al.  A C . elegans genome-scale microRNA network contains composite feedback motifs with high flux capacity , 2008 .

[78]  S. Luo,et al.  Global identification of microRNA–target RNA pairs by parallel analysis of RNA ends , 2008, Nature Biotechnology.

[79]  Yi Zhao,et al.  Clustered microRNAs' coordination in regulating protein-protein interaction network , 2009, BMC Systems Biology.

[80]  Hong Duan,et al.  The regulatory activity of microRNA* species has substantial influence on microRNA and 3′ UTR evolution , 2008, Nature Structural &Molecular Biology.

[81]  Joshua J. Forman,et al.  A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence , 2008, Proceedings of the National Academy of Sciences.

[82]  W. Filipowicz,et al.  Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? , 2008, Nature Reviews Genetics.

[83]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[84]  Dang D. Long,et al.  mirWIP: microRNA target prediction based on microRNA-containing ribonucleoprotein–enriched transcripts , 2008, Nature Methods.

[85]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[86]  R. Place,et al.  MicroRNA-373 induces expression of genes with complementary promoter sequences , 2008, Proceedings of the National Academy of Sciences.

[87]  D. Zack,et al.  Analysis of regulatory network topology reveals functionally distinct classes of microRNAs , 2008, Nucleic acids research.

[88]  E. Cuppen,et al.  Limitations and possibilities of small RNA digital gene expression profiling , 2009, Nature Methods.

[89]  V. Narry Kim,et al.  Functional links between clustered microRNAs: suppression of cell-cycle inhibitors by microRNA clusters in gastric cancer , 2009, Nucleic acids research.

[90]  Webb Miller,et al.  CleaveLand: a pipeline for using degradome data to find cleaved small RNA targets , 2009, Bioinform..

[91]  Yvonne Tay,et al.  MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation , 2009, Nature.

[92]  Martin Reczko,et al.  The database of experimentally supported targets: a functional update of TarBase , 2008, Nucleic Acids Res..

[93]  A. Mele,et al.  Ago HITS-CLIP decodes miRNA-mRNA interaction maps , 2009, Nature.

[94]  Ana M. Aransay,et al.  miRanalyzer: a microRNA detection and analysis tool for next-generation sequencing experiments , 2009, Nucleic Acids Res..

[95]  D. Ganem,et al.  Tandem array–based expression screens identify host mRNA targets of virus-encoded microRNAs , 2009, Nature Genetics.