Open AccessMETTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis
Author(s) -
Rui Su,
Lei Dong,
Yangchan Li,
Min Gao,
P Cody He,
Wei Liu,
Jiangbo Wei,
Zhiyao Zhao,
Lei Gao,
Han Liang,
Xiaolan Deng,
Chenying Li,
Emily Prince,
Brandon Tan,
Ying Qing,
Xi Qin,
Chao Shen,
Min Xue,
Keren Zhou,
Zhenhua Chen,
Jianhuang Xue,
Wei Li,
Hanjun Qin,
Xiwei Wu,
Miao Sun,
Yunsun Nam,
Chun-Wei Chen,
Wendong Huang,
David Horne,
Steven T. Rosen,
Chuan He,
Jianjun Chen
Publication year - 2022
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-021-00835-2
Subject(s) - translation (biology) , microbiology and biotechnology , carcinogenesis , function (biology) , biology , chemistry , computational biology , biochemistry , genetics , cancer , gene , messenger rna
METTL16 has recently been identified as an RNA methyltransferase responsible for the deposition of N 6 -methyladenosine (m 6 A) in a few transcripts. Whether METTL16 methylates a large set of transcripts, similar to METTL3 and METTL14, remains unclear. Here we show that METTL16 exerts both methyltransferase activity-dependent and -independent functions in gene regulation. In the cell nucleus, METTL16 functions as an m 6 A writer to deposit m 6 A into hundreds of its specific messenger RNA targets. In the cytosol, METTL16 promotes translation in an m 6 A-independent manner. More specifically, METTL16 directly interacts with the eukaryotic initiation factors 3a and -b as well as ribosomal RNA through its Mtase domain, thereby facilitating the assembly of the translation-initiation complex and promoting the translation of over 4,000 mRNA transcripts. Moreover, we demonstrate that METTL16 is critical for the tumorigenesis of hepatocellular carcinoma. Collectively, our studies reveal previously unappreciated dual functions of METTL16 as an m 6 A writer and a translation-initiation facilitator, which together contribute to its essential function in tumorigenesis.