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Régulations génétique et moléculaire par ARN interférence chez Trypanosoma brucei

Abstract : RNA interference (RNAi) is a phenomenon discovered in 1998 in which the presence of double-stranded RNA (dsRNA) in a cell leads to degradation of RNA of homologous sequence. RNAi is mediated by a ribonucleoprotein complex that contains short double stranded RNA and a member of a the Argonaute protein family. This thesis is focusing on RNAi in the protist Trypanosoma brucei. We first defined the degree of specificity and efficiency of RNAi generated after expression of dsRNA, parameters that were instrumental in the design of a software allowing selection of dsRNA for silencing experiments. Next, we searched for candidate genes coding for proteins potentially involved in RNAi. The best candidate is TbAGO1, a member of the Argonaute protein family characterised by an extra domain possibly involved in RNA binding. This gene is essential for RNAi. Its deletion leads to significant mitosis defects, that we established were due to defects in spindle formation and chromosome migration. A second phenotype in the absence of RNAi is the overexpression of retroposon (retrotransposons without LTR) transcripts, without a concomitant increase in retroposition. Both phenotypes are independent. We next demonstrated that presence of dsRNA leads to destruction of homologous RNA in the cytoplasm but could also induce transcriptional silencing of the corresponding gene. This type of mechanism could control expression of retroposons but also of genes in which these retro-elements are inserted.
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https://tel.archives-ouvertes.fr/tel-00202018
Contributor : Mickaël Durand-Dubief <>
Submitted on : Thursday, January 3, 2008 - 8:33:44 PM
Last modification on : Friday, January 15, 2021 - 11:30:02 AM
Long-term archiving on: : Thursday, September 27, 2012 - 1:40:10 PM

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  • HAL Id : tel-00202018, version 1

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Mickaël Durand-Dubief. Régulations génétique et moléculaire par ARN interférence chez Trypanosoma brucei. Biochimie [q-bio.BM]. Museum national d'histoire naturelle - MNHN PARIS, 2005. Français. ⟨tel-00202018⟩

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