title: WBSCR22/Merm1 is required for late nuclear pre-ribosomal RNA processing and mediates N7-methylation of G1639 in human 18S rRNA.
abstract: Ribosomal (r)RNAs are extensively modified during ribosome synthesis and their modification is required for the fidelity and efficiency of translation. Besides numerous small nucleolar RNA-guided 2'-O methylations and pseudouridinylations, a number of individual RNA methyltransferases are involved in rRNA modification. WBSCR22/Merm1, which is affected in Williams-Beuren syndrome and has been implicated in tumorigenesis and metastasis formation, was recently shown to be involved in ribosome synthesis, but its molecular functions have remained elusive. Here we show that depletion of WBSCR22 leads to nuclear accumulation of 3'-extended 18SE pre-rRNA intermediates resulting in impaired 18S rRNA maturation. We map the 3' ends of the 18SE pre-rRNA intermediates accumulating after depletion of WBSCR22 and in control cells using 3'-RACE and deep sequencing. Furthermore, we demonstrate that WBSCR22 is required for N(7)-methylation of G1639 in human 18S rRNA in vivo. Interestingly, the catalytic activity of WBSCR22 is not required for 18S pre-rRNA processing, suggesting that the key role of WBSCR22 in 40S subunit biogenesis is independent of its function as an RNA methyltransferase.
authors.affiliation: Centre for Biochemistry and Molecular Cell Biology, Georg-August-University, 37073 Göttingen, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Haag
authors.affiliation: Centre for Biochemistry and Molecular Cell Biology, Georg-August-University, 37073 Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Kretschmer
authors.affiliation: Centre for Biochemistry and Molecular Cell Biology, Georg-August-University, 37073 Göttingen, Germany Göttingen Centre for Molecular Biosciences, Georg-August-University, 37073 Göttingen, Germany Markus.Bohnsack@med.uni-goettingen.de.
authors.forename: Markus T
authors.initials: MT
authors.lastname: Bohnsack
mesh_terms: D001483:Base Sequence; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000502:physiology*; D008969:Molecular Sequence Data; D059367:RNA Cleavage; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012337:RNA, Ribosomal, 18S / Q000235:genetics* / Q000378:metabolism
chemical_list: D012322:RNA Precursors; D012337:RNA, Ribosomal, 18S; C455827:BUD23 protein, human; D008780:Methyltransferases
keywords: RNA modification; Williams–Beuren syndrome; methyltransferase; ribosome