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The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA

Pinto, Rita ; Vågbø, Cathrine B ; Jakobsson, Magnus E LU ; Kim, Yeji ; Baltissen, Marijke P ; O'Donohue, Marie-Françoise ; Guzmán, Ulises H ; Małecki, Jędrzej M ; Wu, Jie and Kirpekar, Finn , et al. (2020) In Nucleic Acids Research 48(2). p.830-846
Abstract

RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem-loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this... (More)

RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem-loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this modification. Accordingly, we found that ZCCHC4 localises to nucleoli, the site of ribosome assembly, and that proteins involved in RNA metabolism are overrepresented in the ZCCHC4 interactome. Interestingly, the absence of m6A4220 perturbs codon-specific translation dynamics and shifts gene expression at the translational level. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nucleic Acids Research
volume
48
issue
2
pages
17 pages
publisher
Oxford University Press
external identifiers
  • pmid:31799605
  • scopus:85077772466
ISSN
1362-4962
DOI
10.1093/nar/gkz1147
language
English
LU publication?
no
additional info
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
id
f7e1a1da-0850-45f2-9fde-72cc8f2346b5
date added to LUP
2020-01-13 08:50:47
date last changed
2024-06-13 09:43:18
@article{f7e1a1da-0850-45f2-9fde-72cc8f2346b5,
  abstract     = {{<p>RNA methylations are essential both for RNA structure and function, and are introduced by a number of distinct methyltransferases (MTases). In recent years, N6-methyladenosine (m6A) modification of eukaryotic mRNA has been subject to intense studies, and it has been demonstrated that m6A is a reversible modification that regulates several aspects of mRNA function. However, m6A is also found in other RNAs, such as mammalian 18S and 28S ribosomal RNAs (rRNAs), but the responsible MTases have remained elusive. 28S rRNA carries a single m6A modification, found at position A4220 (alternatively referred to as A4190) within a stem-loop structure, and here we show that the MTase ZCCHC4 is the enzyme responsible for introducing this modification. Accordingly, we found that ZCCHC4 localises to nucleoli, the site of ribosome assembly, and that proteins involved in RNA metabolism are overrepresented in the ZCCHC4 interactome. Interestingly, the absence of m6A4220 perturbs codon-specific translation dynamics and shifts gene expression at the translational level. In summary, we establish ZCCHC4 as the enzyme responsible for m6A modification of human 28S rRNA, and demonstrate its functional significance in mRNA translation.</p>}},
  author       = {{Pinto, Rita and Vågbø, Cathrine B and Jakobsson, Magnus E and Kim, Yeji and Baltissen, Marijke P and O'Donohue, Marie-Françoise and Guzmán, Ulises H and Małecki, Jędrzej M and Wu, Jie and Kirpekar, Finn and Olsen, Jesper V and Gleizes, Pierre-Emmanuel and Vermeulen, Michiel and Leidel, Sebastian A and Slupphaug, Geir and Falnes, Pål Ø}},
  issn         = {{1362-4962}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{830--846}},
  publisher    = {{Oxford University Press}},
  series       = {{Nucleic Acids Research}},
  title        = {{The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA}},
  url          = {{http://dx.doi.org/10.1093/nar/gkz1147}},
  doi          = {{10.1093/nar/gkz1147}},
  volume       = {{48}},
  year         = {{2020}},
}