The human base excision repair enzyme SMUG1 directly interacts with DKC1 and contributes to RNA quality control

Mol Cell. 2013 Jan 24;49(2):339-45. doi: 10.1016/j.molcel.2012.11.010. Epub 2012 Dec 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleolus / metabolism
  • Coiled Bodies / metabolism
  • Gene Library
  • HeLa Cells
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Polyadenylation
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Transport
  • RNA Processing, Post-Transcriptional*
  • RNA, Ribosomal, 18S / metabolism
  • RNA, Ribosomal, 28S / metabolism
  • RNA, Small Interfering / genetics
  • Uracil-DNA Glycosidase / genetics
  • Uracil-DNA Glycosidase / metabolism*
  • Uridine / analogs & derivatives
  • Uridine / metabolism

Substances

  • Cell Cycle Proteins
  • DKC1 protein, human
  • Nuclear Proteins
  • RNA, Ribosomal, 18S
  • RNA, Ribosomal, 28S
  • RNA, Small Interfering
  • 5-hydroxymethyluridine
  • SMUG1 protein, human
  • Uracil-DNA Glycosidase
  • Uridine