Computational identification of microRNA targets

By Nikolaus Rajewsky, Nicholas D. Socci. Genome Biology, 2004

342 citations recorded by the source corpus.

Recent experiments have shown that the genomes of organisms such as worm, fly, human and mouse encode hundreds of microRNA genes. Many of these microRNAs are thought to regulate the translational expression of other genes by binding to partially complementary sites in messenger RNAs. Phenotypic and expression analysis suggest an important role of microRNAs during development. Therefore, it is of fundamental importance to identify microRNA targets. However, no experimental or computational high-throughput method for target site identification in animals has been published yet. Our main result is a new computational method which is designed to identify microRNA target sites. This method recovers with high specificity known microRNA target sites which previously have been defined experimentally. Based on these results, we present a simple model for the mechanism of microRNA target site recognition. Our model incorporates both kinetic and thermodynamic components of target recognition. When we applied our method to a set of 74 Drosophila melanogaster microRNAs, searching 3' UTR sequences of a predefined set of fly mRNAs for target sites which were evolutionary conserved between Drosophila melanogaster and Drosophila pseudoobscura, we found that a number of key developmental body patterning genes such as hairy and fushi-tarazu are likely to be translationally regulated by microRNAs.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ca3e8f201e7291bd07b35dac5c974d103b20a902

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Citations in the corpus

microRNA Target Predictions across Seven Drosophila Species and Comparison to Mammalian Targets (2005, methodology): “In addition, oogenesis in Drosophila occurs through a very different developmental program than in vertebrates.”
Fast and effective prediction of microRNA/target duplexes. (2004, methodology): “…does not unequivocally mean that these predicted binding sites are not functional, and hairy is evidence to the contrary, as it has been shown in Stark et al. (2003) to be a target of miR-7, and this combination is predicted by Rajewsky and Socci (2004) as well as by our method (E = 0.01, 1/1/0).”
MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype (2007, background): “In humans, at least 10% of the protein-coding mRNAs might be conserved targets of miRNAs [38,39,41-49].”
microPrimer: the biogenesis and function of microRNA (2005, methodology): “…a single target; and (4) lack of a strong secondary structure at the miRNA-binding site on the target (Enright et al., 2003; Lewis et al., 2003; Stark et al., 2003; Kiriakidou et al., 2004; Rajewsky and Socci, 2004; Brennecke et al., 2005; Krek et al., 2005; Lewis et al., 2005; Zhao et al., 2005).”
MiRNA-Directed Regulation of VEGF and Other Angiogenic Factors under Hypoxia (2006, methodology): “The design of FindTar algorithm It was recognized that the nucleus or seed, typically a perfectly Watson-Crick–basepaired stretch of 7 nt starting at either the first or the second base of the microRNA (counted from the 59 end), was the most critical for target recognition [13,14,17].”
A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. (2006, background): “A second group is ‘‘signature-based’’ with the signature derived from the first few nucleotides (typically positions 2 through 8 inclusive) of the microRNA’s 50 region; this signature is referred to as the ‘‘seed’’ or ‘‘nucleus’’ (Krek et al., 2005; Lewis et al., 2003, 2005; Rajewsky and Socci, 2004”
MicroRNA functions in animal development and human disease (2005, background): “…to hundreds of target genes for a given microRNA, based on target predictions using a variety of bioinformatics approaches (Brennecke et al., 2005; John et al., 2004; Kiriakidou et al., 2004; Lewis et al., 2005; Lewis et al., 2003; Rajewsky and Socci, 2004; Stark et al., 2003; Xie et al., 2005).”