TY - BOOK AU - Sirri,V. AU - Grob,A. AU - Berthelet,J. AU - Jourdan,N. AU - Roussel,P. TI - Sirtuin 7 promotes 45S pre-rRNA cleavage at site 2 and determines the processing pathway KW - PRE-RRNA PROCESSING KW - RIBOSOME KW - SIRTINOL KW - SIRT7 KW - NUCLEOLUS KW - DEACETYLASE N2 - 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 the nucleolar NAD+-dependent deacetylase sirtuin 7 in the synthesis of ribosomal subunits, pre-rRNA processing was analyzed after sirtinol-mediated 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 UR - https://drive.google.com/file/d/19XtNBDhigVRs05pV8V8D8AaY71WQjqwN/view?usp=drivesdk ER -