dbSMR: a novel resource of genome-wide SNPs affecting microRNA mediated regulation

BackgroundMicroRNAs (miRNAs) regulate several biological processes through post-transcriptional gene silencing. The efficiency of binding of miRNAs to target transcripts depends on the sequence as well as intramolecular structure of the transcript. Single Nucleotide Polymorphisms (SNPs) can contribute to alterations in the structure of regions flanking them, thereby influencing the accessibility for miRNA binding.DescriptionThe entire human genome was analyzed for SNPs in and around predicted miRNA target sites. Polymorphisms within 200 nucleotides that could alter the intramolecular structure at the target site, thereby altering regulation were annotated. Collated information was ported in a MySQL database with a user-friendly interface accessible through the URL: http://miracle.igib.res.in/dbSMR.ConclusionThe database has a user-friendly interface where the information can be queried using either the gene name, microRNA name, polymorphism ID or transcript ID. Combination queries using 'AND' or 'OR' is also possible along with specifying the degree of change of intramolecular bonding with and without the polymorphism. Such a resource would enable researchers address questions like the role of regulatory SNPs in the 3' UTRs and population specific regulatory modulations in the context of microRNA targets.

[1]  Thomas D. Schmittgen,et al.  The Human Angiotensin II Type 1 Receptor +1166 A/C Polymorphism Attenuates MicroRNA-155 Binding* , 2007, Journal of Biological Chemistry.

[2]  Robert Giegerich,et al.  A comprehensive comparison of comparative RNA structure prediction approaches , 2004, BMC Bioinformatics.

[3]  Lin He,et al.  MicroRNAs: small RNAs with a big role in gene regulation , 2004, Nature Reviews Genetics.

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

[5]  Edwin Wang,et al.  Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers , 2007, Nucleic acids research.

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

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

[8]  Peter F. Stadler,et al.  Thermodynamics of RNA-RNA Binding , 2006, German Conference on Bioinformatics.

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

[10]  N. Rajewsky.  microRNA target predictions in animals , 2006, Nature Genetics.

[11]  V. Scaria,et al.  Host–virus genome interactions: macro roles for microRNAs , 2007, Cellular microbiology.

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

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

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

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

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

[17]  W. Filipowicz,et al.  Repression of protein synthesis by miRNAs: how many mechanisms? , 2007, Trends in cell biology.

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

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

[20]  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.

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

[22]  Andreas Prlic,et al.  Ensembl 2008 , 2007, Nucleic Acids Res..

[23]  A. Hatzigeorgiou,et al.  TarBase: A comprehensive database of experimentally supported animal microRNA targets. , 2005, RNA.

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

[25]  John G Doench,et al.  Specificity of microRNA target selection in translational repression. , 2004, Genes & development.

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

[27]  C. Croce,et al.  miR-15 and miR-16 induce apoptosis by targeting BCL2. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

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