Rôle de la protéine Bcd1p/BCD1 dans les étapes précoces de la biogenèse des snoRNP à boîtes C/D eucaryotes

Abstract : Ribosome biogenesis is especially dependent on the action of small RNA/proteins complexes called small nucleolar ribonucleoproteins (snoRNPs). They are divided into two main families: the so-called box C/D snoRNPs and box H/ACA snoRNPs. Each category performs specific enzymatic processes, 2’-O-methylation and pseudouridylation, respectively, and induces target-specific chemical modification on rRNAs. Few snoRNPs are also essential for pre-rRNA processing. The box C/D snoRNPs are formed by the association of a box C/D snoRNA with a set of four invariant proteins: Snu13p/SNU13, Nop1p/Fibrillarine, Nop56p/NOP56 and Nop58p/NOP58 (yeast/Human). Biogenesis of these RNPs relies on the action of several proteins complexes which constitute a dedicated assembly machinery. Rsa1p/NUFIP, Hit1p/ZNHIT3, and components of the R2TP complex are the best characterized protein actors of this machinery. Additional protein factors probably participate in box C/D snoRNP biogenesis; Bcd1p/ZNHIT6 (Box C/D snoRNA protein 1) is such a candidate as it is essential for the in vivo stability of box C/D snoRNAs, and it was found associated with proteins involved in this machinery in yeast and Human. However, the mechanism governing the recruitment of this protein towards the biogenesis of box C/D snoRNP, and the step of the assembly process relying on the presence of Bcd1p are still unknown. In S. cerevisiae and Human, in vivo and in vitro tools allowed us to improve the understanding of the functions of Bcd1p/ZNHIT6 in box C/D snoRNP assembly. Bcd1p is an assembly factor that is recruited co-transcriptionally on box C/D snoRNA loci, and is required for the recruitment of assembly complexes on nascent snoRNAs. Bcd1p is important for Nop58p association with the assembly factor Rsa1p, which suggests that its primary function is to recruit Nop58p to nascent pre-snoRNPs. This work evidenced important information on the essential role of Bcd1p in C/D snoRNP biogenesis and function
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Submitted on : Monday, November 26, 2018 - 4:56:51 PM
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Arnaud Paul. Rôle de la protéine Bcd1p/BCD1 dans les étapes précoces de la biogenèse des snoRNP à boîtes C/D eucaryotes. Biochimie, Biologie Moléculaire. Université de Lorraine, 2018. Français. ⟨NNT : 2018LORR0148⟩. ⟨tel-01935477⟩

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