Open AccessSirtuin 7 promotes 45S pre-rRNA cleavage at site 2 and determines the processing pathway
Author(s) -
Valentina Sirri,
Alice Grob,
Jérémy Berthelet,
Nathalie Jourdan,
Pascal Roussel
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.228601
Subject(s) - fibrillarin , ribosome biogenesis , biology , sirtuin , nucleolus , microbiology and biotechnology , ribosomal rna , cleavage (geology) , sirtuin 1 , biogenesis , sirt3 , small nucleolar rna , ribosome , nad+ kinase , biochemistry , rna , downregulation and upregulation , gene , enzyme , non coding rna , paleontology , fracture (geology) , cytoplasm
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.