title: The complexity of human ribosome biogenesis revealed by systematic nucleolar screening of Pre-rRNA processing factors.
abstract: Mature ribosomal RNAs (rRNAs) are produced from polycistronic precursors following complex processing. Precursor (pre)-rRNA processing has been extensively characterized in yeast and was assumed to be conserved in humans. We functionally characterized 625 nucleolar proteins in HeLa cells and identified 286 required for processing, including 74 without a yeast homolog. For selected candidates, we demonstrated that pre-rRNA processing defects are conserved in different cell types (including primary cells), defects are not due to activation of a p53-dependent nucleolar tumor surveillance pathway, and they precede cell-cycle arrest and apoptosis. We also investigated the exosome's role in processing internal transcribed spacers (ITSs) and report that 3' end maturation of 18S rRNA involves EXOSC10/Rrp6, a yeast ITS2 processing factor. We conclude that human cells adopt unique strategies and recruit distinct trans-acting factors to carry out essential processing steps, posing fundamental implications for understanding ribosomopathies at the molecular level and developing effective therapeutic agents.
authors: Fonds de la Recherche Scientifique (FRS-FNRS), Université Libre de Bruxelles, 1050 Bruxelles, Belgium.
authors: Lionel
authors: L
authors: Tafforeau
authors: Christiane
authors: C
authors: Zorbas
authors: Jean-Louis
authors: JL
authors: Langhendries
authors: Sahra-Taylor
authors: ST
authors: Mullineux
authors: Vassiliki
authors: V
authors: Stamatopoulou
authors: Romain
authors: R
authors: Mullier
authors: Ludivine
authors: L
authors: Wacheul
authors: Denis L J
authors: DL
authors: Lafontaine
mesh_terms: D017209:Apoptosis; D015152:Blotting, Northern; D059447:Cell Cycle Checkpoints; D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D012322:RNA Precursors; D012335:RNA, Ribosomal; D015534:Trans-Activators; D063326:Exosome Multienzyme Ribonuclease Complex