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Article Dans Une Revue Journal of Cell Science Année : 2019

Sirtuin 7 promotes 45S pre-rRNA cleavage at site 2 and determines the processing pathway

Résumé

In humans, ribosome biogenesis mainly occurs in nucleoli following two alternative pre-rRNA processing pathways differing in the order in which cleavages take place but not by the sites of cleavage. To uncover the role of nucleolar NAD+-dependent deacetylase Sirtuin 7 in the synthesis of ribosomal subunits, pre-rRNA processing was analyzed after sirtinol-inhibition of Sirtuin 7 activity or depletion of Sirtuin 7 protein. We thus reveal that Sirtuin 7 activity is a critical regulator of processing of 45S, 32S and 30S pre-rRNAs. Sirtuin 7 protein is primarily essential to 45S pre-rRNA cleavage at site 2, which is the first step of processing pathway 2. Furthermore, we demonstrate that Sirtuin 7 physically interacts with Nop56 and the GAR domain of fibrillarin, and propose that this could interfere with fibrillarin-dependent cleavage. Sirtuin 7 depletion results in the accumulation of 5’ extended forms of 32S pre-rRNA, and also influences the localization of fibrillarin. Thus, we establish a close relationship between Sirtuin 7 and fibrillarin which might determine the processing pathway used for ribosome biogenesis.

Dates et versions

hal-03975413 , version 1 (06-02-2023)

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Valentina Sirri, Alice Grob, Jérémy Berthelet, Nathalie Jourdan, Pascal Roussel. Sirtuin 7 promotes 45S pre-rRNA cleavage at site 2 and determines the processing pathway. Journal of Cell Science, 2019, ⟨10.1242/jcs.228601⟩. ⟨hal-03975413⟩
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