A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation

By Jianzhao Liu, Y. Yue, Dali Han, Xiao Wang, Ye Fu, Liang Zhang, G. Jia, Miao Yu, Zhike Lu, X. Deng and 3 more. Nature Chemical Biology, 2013

2,948 citations recorded by the source corpus.

N6-methyladenosine (m6A) is the most prevalent and reversible internal modification in mammalian messenger and non-coding RNAs. We report here that human METTL14 catalyzes m6A RNA methylation. Together with METTL3, the only previously known m6A methyltransferase, these two proteins form a stable heterodimer core complex of METTL3-14 that functions in cellular m6A deposition on mammalian nuclear RNAs. WTAP, a mammalian splicing factor, can interact with this complex and affect this methylation.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/278d652fe93ff91d6d9baf4c372f666f97403b81

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Citations in the corpus

Rethinking m6A Readers, Writers, and Erasers (2017, background): “Shortly after these seminal discoveries, the WTAP-METTL3 interaction was confirmed in diverse mammalian cells (Liu et al. 2014, Ping et al. 2014, Schwartz et al. 2014b).”
METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m6A Modification (2017, background): “Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase.”
Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites. (2014, background): “Integrating the proteomic data into a network (Figure 1D; Experimental Procedures) highlights the centrality of WTAP and METTL14 in this complex, consistent with the three recent reports (Liu et al., 2014; Ping et al., 2014; Wang et al., 2014b).”
RNA N6‐methyladenosine methyltransferase‐like 3 promotes liver cancer progression through YTHDF2‐dependent posttranscriptional silencing of SOCS2 (2018, background): “Methyltransferase-like (METTL)3, METTL14, and Wilms’ tumor 1-associating protein (WTAP) are the core components of this complex.((14-16)) Both METTL3 and METTL14 contain an S-adenosyl methionine-binding motif.”
YTH Domain: A Family of N6-methyladenosine (m6A) Readers (2018, background): “Similar to other epigenetic modifications, m(6)A is dynamic and reversible, established mainly by the METTL3–METTL14 methyltransferase complex [20,21] and removed by demethylases including the fat mass and obesity-associated protein (FTO) [22] and AlkB homolog 5 RNA demethylase (ALKBH5) [23].”
UniProt: a worldwide hub of protein knowledge (2018, background): “Methyltransferase activity has been reported for both (19).”