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Ignatova, V.V. ; Stolz, P.* ; Kaiser, S.* ; Gustafsson, T.H.* ; Lastres, P.R.* ; Sanz-Moreno, A. ; Cho, Y.-L. ; Amarie, O.V.* ; Aguilar-Pimentel, J.A. ; Klein-Rodewald, T. ; Calzada-Wack, J. ; Becker, L. ; Marschall, S. ; Kraiger, M. ; Garrett, L. ; Seisenberger, C. ; Hölter, S.M. ; Borland, K.* ; Van De Logt, E.* ; Jansen, P.W.T.C.* ; Baltissen, M.P.* ; Valenta, M. ; Vermeulen, M.* ; Wurst, W. ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; Rando, O.J.* ; Kellner, S.M.* ; Bultmann, S.* ; Schneider, R.

The rRNA m6A methyltransferase METTL5 is involved in pluripotency and developmental programs.

Genes Dev. 34, 715-729 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Covalent chemical modifications of cellular RNAs directly impact all biological processes. However, our mechanistic understanding of the enzymes catalyzing these modifications, their substrates and biological functions, remains vague. Amongst RNA modifications N6-methyladenosine (m6A) is widespread and found in messenger (mRNA), ribosomal (rRNA), and noncoding RNAs. Here, we undertook a systematic screen to uncover new RNA methyltransferases. We demonstrate that the methyltransferase-like 5 (METTL5) protein catalyzes m6A in 18S rRNA at position A1832 We report that absence of Mettl5 in mouse embryonic stem cells (mESCs) results in a decrease in global translation rate, spontaneous loss of pluripotency, and compromised differentiation potential. METTL5-deficient mice are born at non-Mendelian rates and develop morphological and behavioral abnormalities. Importantly, mice lacking METTL5 recapitulate symptoms of patients with DNA variants in METTL5, thereby providing a new mouse disease model. Overall, our biochemical, molecular, and in vivo characterization highlights the importance of m6A in rRNA in stemness, differentiation, development, and diseases.
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Publication type Article: Journal article
Document type Scientific Article
Keywords M6a ; Methyltransferase ; Pluripotency; Nucleotide Resolution; Xenopus-laevis; Messenger-rna; Wide Analysis; Methyl-groups; Translation; Platform; Quantification; Identification; Locations
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 0890-9369
e-ISSN 1549-5477
Journal Genes and Development
Quellenangaben Volume: 34, Issue: 9-10, Pages: 715-729 Article Number: , Supplement: ,
Publisher Cold Spring Harbor Laboratory Press
Publishing Place 1 Bungtown Rd, Cold Spring Harbor, Ny 11724 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Functional Epigenetics (IFE)
Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30201 - Metabolic Health
30204 - Cell Programming and Repair
Research field(s) Helmholtz Diabetes Center
Genetics and Epidemiology
PSP Element(s) G-502800-001
G-500600-001
G-500692-001
G-500500-001
DOI 10.1101/gad.333369.119
WOS ID WOS:000530651500009
Scopus ID 85084961210
PubMed ID 32217665
Erfassungsdatum 2020-04-01
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