PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Schöller, E.* ; Weichmann, F.* ; Treiber, T.* ; Ringle, S.* ; Treiber, N.* ; Flatley, A. ; Feederle, R. ; Bruckmann, A.* ; Meister, G.*

Interactions, localization, and phosphorylation of the m6A generating METTL3–METTL14–WTAP complex.

RNA 24, 499-512 (2018)
Verlagsversion Postprint DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
N6-methyladenine (m6A) is found on many eukaryotic RNAs including mRNAs. m6A modification has been implicated in mRNA stability and turnover, localization, or translation efficiency. A heterodimeric enzyme complex composed of METTL3 and METTL14 generates m6A on mRNAs. METTL3/14 is found in the nucleus where it is localized to nuclear speckles and the splicing regulator WTAP is required for this distinct nuclear localization pattern. Although recent crystal structures revealed how the catalytic MT-A70 domains of METTL3 and METTL14 interact with each other, a more global architecture including WTAP and RNA interactions has not been reported so far. Here, we used recombinant proteins and mapped binding surfaces within the METTL3/14-WTAP complex. Furthermore, we identify nuclear localization signals and identify phosphorylation sites on the endogenous proteins. Using an in vitro methylation assay, we confirm that monomeric METTL3 is soluble and inactive while the catalytic center of METTL14 is degenerated and thus also inactive. In addition, we show that the C-terminal RGG repeats of METTL14 are required for METTL3/14 activity by contributing to RNA substrate binding. Our biochemical work identifies characteristic features of METTL3/14-WTAP and reveals novel insight into the overall architecture of this important enzyme complex.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.490
0.940
128
202
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter M6a ; Methyltransferase ; Mettl14 ; Mettl3 ; Rna Modification; Gene-expression Regulation; Messenger-rna Methylation; N-6-adenosine Methylation; Nuclear-rna; Translation; Protein; N6-methyladenosine; Methyltransferase; Identification; Demethylase
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 1355-8382
e-ISSN 1469-9001
Zeitschrift RNA
Quellenangaben Band: 24, Heft: 4, Seiten: 499-512 Artikelnummer: , Supplement: ,
Verlag Cold Spring Harbor Laboratory Press
Verlagsort Cold Spring Harbor
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502210-001
DOI 10.1261/rna.064063.117
WOS ID WOS:000428085200006
Scopus ID 85044966647
PubMed ID 29348140
Erfassungsdatum 2018-03-20
[➜Korrektur melden]