Pinto, Rita; Vågbø, Cathrine B; Jakobsson, Magnus E; Kim, Yeji; Baltissen, Marijke P; O’Donohue, Marie-Françoise; Guzmán, Ulises H; Małecki, Jędrzej M; Wu, Jie; Kirpekar, Finn; Olsen, Jesper V; Gleizes, Pierre-Emmanuel; Vermeulen, Michiel; Leidel, Sebastian A; Slupphaug, Geir; Falnes, Pål Ø (2020). The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA. Nucleic acids research, 48(2), pp. 830-846. Oxford University Press 10.1093/nar/gkz1147
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Kim, Ye Ji, Wu, Jie, Leidel, Sebastian Andreas |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
0305-1048 |
Publisher: |
Oxford University Press |
Language: |
English |
Submitter: |
Christina Schüpbach |
Date Deposited: |
13 Jan 2020 08:32 |
Last Modified: |
05 Dec 2022 15:34 |
Publisher DOI: |
10.1093/nar/gkz1147 |
PubMed ID: |
31799605 |
BORIS DOI: |
10.7892/boris.137056 |
URI: |
https://boris.unibe.ch/id/eprint/137056 |
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