MicroSNiPer: a web tool for prediction of SNP effects on putative microRNA targets

MicroRNAs are short, approximately 22 nucleotide noncoding RNAs binding to partially complementary sites in the 3′UTR of target mRNAs. This process generally results in repression of multiple targets by a particular microRNA. There is substantial interest in methods designed to predict the microRNA targets and effect of single nucleotide polymorphisms (SNPs) on microRNA binding, given the impact of microRNA on posttranscriptional regulation and its potential relation to complex diseases. We developed a web‐based application, MicroSNiPer, which predicts the impact of a SNP on putative microRNA targets. This application interrogates the 3′‐untranslated region and predicts if a SNP within the target site will disrupt/eliminate or enhance/create a microRNA binding site. MicroSNiPer computes these sites and examines the effects of SNPs in real time. MicroSNiPer is a user‐friendly Web‐based tool. Its advantages include ease of use, flexibility, and straightforward graphical representation of the results. It is freely accessible at http://cbdb.nimh.nih.gov/microsniper. Hum Mutat 31:–11, 2010. © 2010 Wiley‐Liss, Inc.

[1]  H. Lipkin Where is the ?c? , 1978 .

[2]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[3]  E. Lai Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation , 2002, Nature Genetics.

[4]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

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

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

[7]  Eun-Young Choi,et al.  The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3'UTR. , 2004, Genes & development.

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

[9]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

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

[11]  Murat Gunel,et al.  Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome , 2005, Science.

[12]  R. Russell,et al.  Principles of MicroRNA–Target Recognition , 2005, PLoS biology.

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

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

[15]  Peter F. Stadler,et al.  Memory Efficient Folding Algorithms for Circular RNA Secondary Structures , 2006, German Conference on Bioinformatics.

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

[17]  Oliver Hobert,et al.  Perfect seed pairing is not a generally reliable predictor for miRNA-target interactions , 2006, Nature Structural &Molecular Biology.

[18]  N. Rajewsky,et al.  Natural selection on human microRNA binding sites inferred from SNP data , 2006, Nature Genetics.

[19]  Florian Caiment,et al.  A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep , 2006, Nature Genetics.

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

[21]  Praveen Sethupathy,et al.  Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. , 2007, American journal of human genetics.

[22]  Carole Ober,et al.  Allele-specific targeting of microRNAs to HLA-G and risk of asthma. , 2007, American journal of human genetics.

[23]  Wen-Hsiung Li,et al.  Human polymorphism at microRNAs and microRNA target sites , 2007, Proceedings of the National Academy of Sciences.

[24]  Ligang Wu,et al.  PolymiRTS Database: linking polymorphisms in microRNA target sites with complex traits , 2006, Nucleic Acids Res..

[25]  B. White,et al.  The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. , 2007, Molecular endocrinology.

[26]  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.

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

[28]  D. Banerjee,et al.  A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance , 2007, Proceedings of the National Academy of Sciences.

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

[30]  Lawrence S. Hon,et al.  The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression , 2007, Genome Biology.

[31]  B. White,et al.  The Micro-Ribonucleic Acid (miRNA) miR-206 Targets the Human Estrogen Receptor-α (ERα) and Represses ERα Messenger RNA and Protein Expression in Breast Cancer Cell Lines , 2007 .

[32]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[33]  Zhaohui S. Qin,et al.  A second generation human haplotype map of over 3.1 million SNPs , 2007, Nature.

[34]  Praveen Sethupathy,et al.  MicroRNA target site polymorphisms and human disease. , 2008, Trends in genetics : TIG.

[35]  Stijn van Dongen,et al.  miRBase: tools for microRNA genomics , 2007, Nucleic Acids Res..

[36]  Gaofeng Wang,et al.  Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. , 2008, American journal of human genetics.

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

[38]  P. Whorwell,et al.  First evidence for an association of a functional variant in the microRNA-510 target site of the serotonin receptor-type 3E gene with diarrhea predominant irritable bowel syndrome. , 2008, Human molecular genetics.

[39]  Sanghyuk Lee,et al.  miRGator: an integrated system for functional annotation of microRNAs , 2007, Nucleic Acids Res..

[40]  Chao Cheng,et al.  Inferring MicroRNA Activities by Combining Gene Expression with MicroRNA Target Prediction , 2008, PloS one.

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

[42]  Ye Ding,et al.  Analysis of Microrna-Target Interactions by a Target Structure Based Hybridization Model , 2007, Pacific Symposium on Biocomputing.

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

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

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

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

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

[48]  A. T. Freitas,et al.  Current tools for the identification of miRNA genes and their targets , 2009, Nucleic acids research.

[49]  T. Conner,et al.  A common polymorphism in serotonin receptor 1B mRNA moderates regulation by miR-96 and associates with aggressive human behaviors , 2009, Molecular Psychiatry.

[50]  I. Kohane,et al.  Tissue and Process Specific microRNA–mRNA Co-Expression in Mammalian Development and Malignancy , 2009, PloS one.

[51]  I. Kohane,et al.  Correction: Tissue and Process Specific microRNA–mRNA Co-Expression in Mammalian Development and Malignancy , 2009, PLoS ONE.

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

[53]  Michel Georges,et al.  Patrocles: a database of polymorphic miRNA-mediated gene regulation in vertebrates , 2008, Nucleic Acids Res..