An highly accurate method for the identification of bona-fide microRNAs targets within mammalian genes
MREdictor tool

MREdictor is an highly accurate method for the identification of bona-fide microRNAs targets within mammalian genes. MREdictor method shown the highest accuracy when compared to state-of-the-art methods, and allowed the identification of novel non-canonical and Pumilio-dependent microRNAs targets.

Main improvements introduced by this method, compared to state-of-the-art algorithms, are:

1) MREdictor takes in to account the pairing between miRNA and its cognate MRE is a two-step process that starts from the seed-match and extends to the miRNA 3'-end. Structural evidence shows that the miRNA 5'-end is anchored in a solventaccessible binding pocket within the MID domain of Ago proteins, whereas the 3'-end is solvent inaccessible and locked in a binding pocket of the PAZ domain (Wang et al., 2008;Frank et al., 2010;Lambert et al., 2011). Binding of the miRNA 5'-end to its cognate mRNA leads to a conformational change, with the subsequent release of its 3'-end from the PAZ domain leading to a productive pairing.
To account for this mechanism, instead of using a Smith-Waterman approach, which maximizes only the interactions between the miRNA and MRE, MREdictor simulates the duplex formation as a two-step reaction of duplex nucleation at the seed level with progressive pairing under the constraints imposed by the seed. Compared with the Smith?Waterman approach, this method considers the seed-constraint compliant structure, which minimizes both the duplex free energy and the free energy of the MRE rearranged tointeract with the miRNA and maximizes the duplex bonds. This approach to microRNA-mRNA pairing simulation, increases the accuracy of targets prediction, and allows the idenfication of non-canonical targets.

2) MREdictor considers that stable secondary structures within the 3'-UTR of a mRNA can prevent the productive pairing of microRNAs, and Pumilio RNA Binding Proteins can open such structures in order to allow the microRNA to pair. MREdictor algorithm evaluates the local accessibility of the target mRNA at the level of the microRNA pairing region. Sites predicted to be accessible, or inaccessible but presenting a nearby Pumilio proteins recognition element, are kept by the algorithm, while all other sites are discarded.

For more informations about MREdictor, you can read the paper on NAR

The web version of the algorithm is available at: http://mredictor.hugef-research.org