The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112.
Adenosine
/ chemistry
Base Sequence
Binding Sites
CRISPR-Associated Protein 9
/ genetics
CRISPR-Cas Systems
Cell Line, Tumor
Crystallography, X-Ray
Gene Deletion
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Methyltransferases
/ chemistry
Models, Molecular
Nucleic Acid Conformation
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Stability
RNA, Guide, Kinetoplastida
/ genetics
RNA, Messenger
/ chemistry
RNA, Ribosomal, 18S
/ chemistry
Signal Transduction
Substrate Specificity
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
05 09 2019
05 09 2019
Historique:
accepted:
12
07
2019
revised:
14
06
2019
received:
09
04
2019
pubmed:
23
7
2019
medline:
4
12
2019
entrez:
23
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31328227
pii: 5536363
doi: 10.1093/nar/gkz619
pmc: PMC6735865
doi:
Substances chimiques
RNA, Guide
0
RNA, Messenger
0
RNA, Ribosomal, 18S
0
METTL5 protein, human
EC 2.1.1.-
Methyltransferases
EC 2.1.1.-
TRMT112 protein, human
EC 2.1.1.-
rRNA (adenosine-O-2'-)methyltransferase
EC 2.1.1.230
CRISPR-Associated Protein 9
EC 3.1.-
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7719-7733Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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