Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex

By Xiang Wang, Jing Feng, Yuan Xue, Z. Guan, Delin Zhang, Zhu Liu, Z. Gong, Qiang Wang, Jinbo Huang, Chun Tang and 2 more. Nature, 2016

1,068 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/70474e94d98a5549d8235d908fcfa4de2807c910

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Citations in the corpus

Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d (2018, background): “Recent crystal structural studies investigated themolecular activities of the two predicted methyltransferases METTL3 and METTL14 (Sledz and Jinek 2016; Wang et al. 2016a,b).”
Zc3h13 regulates nuclear RNA m6A methylation and mouse embryonic stem cell self-renewal (2018, background): “The crystal structure of the METTL3 and METTL14 complex suggests that METTL3 is the catalytic component while METTL14, which forms a heterodimer with METTL3, contributes to substrate RNA binding (Wang et al., 2016a; Wang et al., 2016b).”
UniProt: a worldwide hub of protein knowledge (2018, background): “Subsequent structural studies have now shown that that only one protein, METTL3, constitutes the catalytic subunit (20–22).”
YTH Domain: A Family of N6-methyladenosine (m6A) Readers (2018, background): “Although both METTL3 and METTL14 adopt a canonical fold similar to that of other methyltransferases [20], only METTL3 can bind to the methyl donor Sadenosyl methionine (SAM or AdoMet), whereas METTL14 acts to modulate the activity of METTL3 and binds to the RNA substrate instead [20,24,25].”
Where, when and how: context-dependent functions of RNA methylation writers, readers, and erasers (2019, background): “…a stable core complex formed between methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) (Bokar et al., 1997; Liu et al., 2013)— the former as the catalytic subunit and the latter as an essential component to facilitate RNA binding (Wang et al., 2016a; Wang et al., 2016b).”
METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m6A Modification (2017, background): “…of wild-type (METTL14-WT), but not mutated METTL14 (METTL14-R298P; R298 is critical for target recognition of the methyltransferase complex [Wang et al., 2016a, 2016b]), substantially increased global m6A level and promoted cell immortalization mediated by MA9 (Figures 3B and 3C),…”
m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer (2018, positive): “Crystal structures of the METTL3-METTL14 complex reveal that the R298 residue lies in the putative RNA-binding groove at the interface between the two subunits 37–39 .”
Rethinking m6A Readers, Writers, and Erasers (2017, background): “R298P, which is detected in uterine/ endometrial cancers, is a mutation in the RNA-binding domain, and the mutated form of METTL14 shows partially reduced methyltransferase activity, most likely due to inefficient RNA binding (P. Wang et al. 2016).”
Methylation multiplicity and its clinical values in cancer (2021, positive): “METTL14 could enhance the catalytic activity of METTL3 via forming heterodimers with METTL3 with the ratio of 1:1 (Refs 21, 22).”