title: The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis.
abstract: At the heart of the ribosome lie rRNAs, whose catalytic function in translation is subtly modulated by posttranscriptional modifications. In the small ribosomal subunit of budding yeast, on the 18S rRNA, two adjacent adenosines (A1781/A1782) are N(6)-dimethylated by Dim1 near the decoding site, and one guanosine (G1575) is N(7)-methylated by Bud23-Trm112 at a ridge between the P- and E-site tRNAs. Here we establish human DIMT1L and WBSCR22-TRMT112 as the functional homologues of yeast Dim1 and Bud23-Trm112. We report that these enzymes are required for distinct pre-rRNA processing reactions leading to synthesis of 18S rRNA, and we demonstrate that in human cells, as in budding yeast, ribosome biogenesis requires the presence of the modification enzyme rather than its RNA-modifying catalytic activity. We conclude that a quality control mechanism has been conserved from yeast to human by which binding of a methyltransferase to nascent pre-rRNAs is a prerequisite to processing, so that all cleaved RNAs are committed to faithful modification. We further report that 18S rRNA dimethylation is nuclear in human cells, in contrast to yeast, where it is cytoplasmic. Yeast and human ribosome biogenesis thus have both conserved and distinctive features.
authors: RNA Molecular Biology, Fonds de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.
authors: Christiane
authors: C
authors: Zorbas
authors: RNA Molecular Biology, Fonds de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.
authors: Emilien
authors: E
authors: Nicolas
authors: RNA Molecular Biology, Fonds de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium.
authors: Ludivine
authors: L
authors: Wacheul
authors: Centre National de la Recherche Scientifique FRE3630, Institut de Biologie Physico-Chimique, Paris F-75005, France.
authors: Emmeline
authors: E
authors: Huvelle
authors: Centre National de la Recherche Scientifique FRE3630, Institut de Biologie Physico-Chimique, Paris F-75005, France.
authors: Valérie
authors: V
authors: Heurgué-Hamard
authors: RNA Molecular Biology, Fonds de la Recherche Scientifique (FRS/FNRS), Université Libre de Bruxelles, B-6041 Charleroi-Gosselies, Belgium Center for Microscopy and Molecular Imaging, B-6041 Charleroi-Gosselies, Belgium denis.lafontaine@ulb.ac.be.
authors: Denis L J
authors: DL
authors: Lafontaine
mesh_terms: D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012337:RNA, Ribosomal, 18S / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D012322:RNA Precursors; D012337:RNA, Ribosomal, 18S; C455827:BUD23 protein, human; C000605619:DIMT1 protein, human; D008780:Methyltransferases; C000605620:TRMT112 protein, human