Influence of pre-mirna compositional properties on RISC complex recruitment and target selec- tion. Arrigo P (1) ., Mitra C (2) . , and Izzotti A (3) . (1) CNR ISMAC Via De Marini 6 16149 Genova Italy phone:+39-010-6475882 email:arrigo@ge.ismac.cnr.it (2) University of Hyderabad Dept of Biochemistry,500046 Hyderabad Indi (3) University of Genoa, Dept of Health Science Via A. Pastore 1 16132 Genova Italy ABSTRACT The mirna targets detection is a key goal of computational biology. This class of non-coding RNA have acquired appreciable importance in understanding molecular mechanism of diseas- es. In this paper we have investigated the rela- tions between compositional fetures of microrna precursors and the target recognition of corre- sponding mature micrornas. In particular we want to determine the role of methylation on precursors. An increasing set of experimental evidences corroborate the hypothesis that mi- croRNA methylation can be associated with pathological condition. Altered microRNA meth- ylation seems to be associated with different can- cers In order to predict the set of microrna prone to methylation we have analysed the human pre- cursors available in the MicroRNA registry re- lease 16.0. Our analysis principally has been centered on compositional asymmetries correlat- ed with the CG content. Unequal distribution of dinucleotide has been investigate at genomic lev- el (CpG island) of region potentially coding mir- na. The role of inhomogeneous distribution of CG in pre-mirna is not yet deeply analysed. It possible that the different frequency of these nu- cleotides can play a role both in mirna matura- tion process and/or DNA methylation. Our anal- ysis has identified two extremal group of human pre-mirna: one that have high content of CG di- nucleotides and the second lack of CG The role compositional characteristics of mirnas. In particular premirna lacking CG dinucleotides seems to be involved in regulation of critical pro- cesses such gene transcription. Among these precursor we investigated the potential targets of hsa-let7a-1. on oxidative stress. 1. INTRODUCTION MiRNAs represent an evolutionarily conserved class of small non-coding RNAs. These molecules have been ascertained in many eukaryotes, both plants and animals, but also in several viruses. MiRNAs are considered one of the factors that in- crease the architectural complexity of organisms. The origin of miRNAs is not yet fully elucidated, probably their emergence is due to a massive du- plication of genes. Several experimental findings seem to corroborate this hypothesis. The main role of miRNAs is the control of gene expression at post-trascriptional level. In the last decade non- coding RNAs (ncRNAs) and, in particular, the miRNAs, have acquired a great notability for the interpretation of the mechanisms leading to mo- lecular pathogenesis. An increasing number of ex- periments have demonstrated that variations of miRNA expression profile are associated with pathological conditions such as cancer or cardio- vascular diseases. A pharmacological therapy or the effect of toxic compounds could also cause changes of miRNA expression. MiRNA sensitivi- ty to endogenous and exogenous factors make them particularly promising for diagnostic and therapeutic applications. It has been estimated that miRNAs could control about 30% of human genes. It is widely accepted that a miRNA could inhibit post-trascriptional gene expression interact- ing with specific nucleotide ‘motifs’ in the 3’UTR of a target mRNA. The relation, between miRNAs and their targets, is a one-to-many relation. A sin- gle miRNA could potentially inhibit hundreds of different mRNAs. A reliable identification of