ARAUD Tanguy Hors Thèse

Département de Microbiologie et Médecine MoléculaireCentre Médicale UniversitaireOverview of the miRNA pathwaysby Tanguy ARAUDHors Thèse ManuscriptCo-directeurs de thèse: Dr J. CURRAN (CMU) Pr J.D. ROCHAIX (Science III)Examinateur: Pr D. BELIN (CMU) Pr W. REITH (CMU)Novembre 2008Overview of the miRNA pathwaysIndexOnce upon a time… 3What’s a microRNA? 4Universal nomenclature 5Genetic organisation and transcription 7miRNA Biogenesis 8Nuclear processing: Cleavage by the Drosha-DGCR8 Complex 8Nuclear export 10Cytoplasmic procy DICER 10Incorporation into RISC and activation 11Biological activity 12Translational inhibition at the elongation step. 13Translational inhibition at the initiation step 15Indirect degradation 15Translational activation 16Regulation of microRNA activity 16Disease 17miRNAs and cancer 17Viral infection and host defence 18Heart disease 20Conclusion 20Acknowledgements 21Bibliographie 21Hors-Thèse Tanguy ARAUD Page 2Overview of the miRNA pathwaysOnce upon a time…The micro RNA (miRNA) story started in the mid 1970’s with the isolation of a mutation (e912) in Caenorhabditis elegans (C. elegans) (Hodgkin, 1974). This mutation affected the lin-4 gene. It blocked ventral hypodermal cell division during development and generated a “Vulvaless” phenotype (Horvitz and Sulston, 1980) (figure1). It appeared that the e912 mutation was causing a failure of temporal development, indicating that lin-4 might encode a ...