title: The human base excision repair enzyme SMUG1 directly interacts with DKC1 and contributes to RNA quality control.
abstract: Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1) is a base excision repair enzyme that removes uracil and oxidised pyrimidines from DNA. We show that SMUG1 interacts with the pseudouridine synthase Dyskerin (DKC1) and colocalizes with DKC1 in nucleoli and Cajal bodies. As DKC1 functions in RNA processing, we tested whether SMUG1 excised modified bases in RNA and demonstrated that SMUG1 has activity on single-stranded RNA containing 5-hydroxymethyldeoxyuridine, but not pseudouridine, the nucleoside resulting from isomerization of uridine by DKC1. Moreover, SMUG1 associates with the 47S rRNA precursor processed by DKC1, and depletion of SMUG1 leads to a reduction in the levels of mature rRNA accompanied by an increase in polyadenylated rRNA. Depletion of SMUG1, and, in particular, the combined loss of SMUG1 and DKC1, leads to accumulation of 5-hydroxymethyluridine in rRNA. In conclusion, SMUG1 is a DKC1 interaction partner that contributes to rRNA quality control, partly by regulating 5-hydroxymethyluridine levels.
authors.affiliation: The Biotechnology Centre, University of Oslo, Blindern, 0317 Oslo, Norway.
authors.forename: Laure
authors.initials: L
authors.lastname: Jobert
authors.forename: Hanne K
authors.initials: HK
authors.lastname: Skjeldam
authors.forename: Bjørn
authors.initials: B
authors.lastname: Dalhus
authors.forename: Anastasia
authors.initials: A
authors.lastname: Galashevskaya
authors.forename: Cathrine Broberg
authors.initials: CB
authors.lastname: Vågbø
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
authors.forename: Hilde
authors.initials: H
authors.lastname: Nilsen
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism; D020541:Coiled Bodies / Q000378:metabolism; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D026723:Polyadenylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D012323:RNA Processing, Post-Transcriptional; D012337:RNA, Ribosomal, 18S / Q000378:metabolism; D012339:RNA, Ribosomal, 28S / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051981:Uracil-DNA Glycosidase / Q000235:genetics / Q000378:metabolism*; D014529:Uridine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C112148:DKC1 protein, human; D009687:Nuclear Proteins; D012337:RNA, Ribosomal, 18S; D012339:RNA, Ribosomal, 28S; D034741:RNA, Small Interfering; C012367:5-hydroxymethyluridine; C498095:SMUG1 protein, human; D051981:Uracil-DNA Glycosidase; D014529:Uridine