Crystal structure of human METTL5-TRMT112 complex, the 18S rRNA m6A1832 methyltransferase at 1.6A resolution
Classification:
TRANSFERASE
Technique:
X-Ray Diffraction
Resolution:
1.6
R value free:
0.215
R value observed:
0.187
R value work:
0.186
Abstract of the PDB Structure's related Publication:
N6-methyladenosine (m6A) has recently been found abundantly on messenger RNA and shown to regulate most steps of mRNA metabolism. Several important m6A methyltransferases have been described functionally and structurally, but the enzymes responsible for installing one m6A residue on each subunit of human ribosomes at functionally important sites have eluded identification for over 30 years. Here, we identify METTL5 as the enzyme responsible for 18S rRNA m6A modification and confirm ZCCHC4 as the 28S rRNA modification enzyme. We show that METTL5 must form a heterodimeric complex with TRMT112, a known methyltransferase activator, to gain metabolic stability in cells. We provide the first atomic resolution structure of METTL5-TRMT112, supporting that its RNA-binding mode differs distinctly from that of other m6A RNA methyltransferases. On the basis of similarities with a DNA methyltransferase, we propose that METTL5-TRMT112 acts by extruding the adenosine to be modified from a double-stranded nucleic acid.
The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112.
Nhan van Tran,Felix G M Ernst,Ben R Hawley,Christiane Zorbas,Nathalie Ulryck,Philipp Hackert,Katherine E Bohnsack,Markus T Bohnsack,Samie R Jaffrey,Marc Graille,Denis L J Lafontaine
The rRNA mA methyltransferase METTL5 is involved in pluripotency and developmental programs.
Valentina V Ignatova,Paul Stolz,Steffen Kaiser,Tobias H Gustafsson,Palma Rico Lastres,Adrián Sanz-Moreno,Yi-Li Cho,Oana V Amarie,Antonio Aguilar-Pimentel,Tanja Klein-Rodewald,Julia Calzada-Wack,Lore Becker,Susan Marschall,Markus Kraiger,Lillian Garrett,Claudia Seisenberger,Sabine M Hölter,Kayla Borland,Erik Van De Logt,Pascal W T C Jansen,Marijke P Baltissen,Magdalena Valenta,Michiel Vermeulen,Wolfgang Wurst,Valerie Gailus-Durner,Helmut Fuchs,Martin Hrabe de Angelis,Oliver J Rando,Stefanie M Kellner,Sebastian Bultmann,Robert Schneider