Objetivo MicroRNAs are a recently discovered class of small non-coding RNAs that act as post-transcriptional regulators of gene expression by silencing target mRNAs. They have wide ranging roles in many cellular processes including cellular proliferation, stress response, apoptosis, development and differentiation. Altered expression of microRNA has been implicated in tumorigenesis, and microRNAs are recognised as modulating factors in numerous cancers including gastric cancer, lung cancer and lymphocytic leukaemia. Specifically, microRNA functions within the cytoplasm in concert with the human-induced silencing complex by binding the 3’ untranslated region of the target mRNA. This binding to target mRNA effectively inhibits expression of the protein, and thus mediates the gene silencing effect of microRNA. This project aims to elucidate the structure and biophysical basis of the nuclear export complex formed by pre-microRNA (precursor of microRNA), RanGTP and exportin-5. These goals will be achieved using a combination of structural, biochemical and biophysical approaches. X-ray crystallography and nuclear magnetic resonance will be utilised to study the structure of the export complex of microRNA. In parallel with the determination of the complex structure, the key residues involved in complex formation will be identified by mutagenesis, cross-linking and further NMR approaches. Furthermore, a range of biophysical techniques will be employed to study the thermodynamic and kinetic basis for the formation of the microRNA export complex. The information provided by this study will be of the highest international standard and will open novel avenues to therapeutic design as well as represent a significant advance in our understanding of cellular biology. Importantly, it will provide a platform for knowledge sharing and collaboration between a European based organization and a top-class non European researcher. Ámbito científico medical and health sciencesclinical medicineoncologylung cancernatural sciencesearth and related environmental sciencesgeologymineralogycrystallographynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesclinical medicineoncologyleukemia Palabras clave Cancer Crystallography MicroRNA NMR Nuclear Export Structural Biology Programa(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) PEOPLE-2007-4-2.IIF - Marie Curie Action: "International Incoming Fellowships" Convocatoria de propuestas FP7-PEOPLE-2007-4-2-IIF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IIF - International Incoming Fellowships (IIF) Coordinador MEDICAL RESEARCH COUNCIL Aportación de la UE € 171 091,96 Dirección 20 Park Crescent W1B 1AL LONDON Reino Unido Ver en el mapa Tipo de actividad Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Contacto administrativo Elizabeth Cutler (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos