@article{a037493a35614443b9c144a045d0cc7f,
title = "METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis",
abstract = "METTL16 has recently been identified as an RNA methyltransferase responsible for the deposition of N6-methyladenosine (m6A) 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 m6A writer to deposit m6A into hundreds of its specific messenger RNA targets. In the cytosol, METTL16 promotes translation in an m6A-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 m6A writer and a translation-initiation facilitator, which together contribute to its essential function in tumorigenesis.",
author = "Rui Su and Lei Dong and Yangchan Li and Min Gao and He, {P. Cody} and Wei Liu and Jiangbo Wei and Zhicong Zhao and Lei Gao and Li Han and Xiaolan Deng and Chenying Li and Emily Prince and Brandon Tan and Ying Qing and Xi Qin and Chao Shen and Meilin Xue and Keren Zhou and Zhenhua Chen and Jianhuang Xue and Wei Li and Hanjun Qin and Xiwei Wu and Miao Sun and Yunsun Nam and Chen, {Chun Wei} and Wendong Huang and David Horne and Rosen, {Steven T.} and Chuan He and Jianjun Chen",
note = "Funding Information: We thank N. K. Conrad for providing pcDNA3-METTL16, pcDNA3-METTL16-PP185/186AA and METTL16-F187G. This work was supported in part by the US National Institutes of Health grant nos CA243386 (J.C.), R01 CA214965 (J.C.), R01 CA236399 (J.C.), R01 CA211614 (J.C.), R01 DK124116 (J.C.), RM1 HG008935 (C.H.) and R01 CA139158 (W.H.), The Simms/Mann Family Foundation (J.C.) and The Margaret Early Medical Research Trust (R.S.). J.C. is a Leukemia and Lymphoma Society (LLS) Scholar. C.H. is an investigator of the Howard Hughes Medical Institute. Funding Information: We thank N. K. Conrad for providing pcDNA3-METTL16, pcDNA3-METTL16-PP185/186AA and METTL16-F187G. This work was supported in part by the US National Institutes of Health grant nos CA243386 (J.C.), R01 CA214965 (J.C.), R01 CA236399 (J.C.), R01 CA211614 (J.C.), R01 DK124116 (J.C.), RM1 HG008935 (C.H.) and R01 CA139158 (W.H.), The Simms/Mann Family Foundation (J.C.) and The Margaret Early Medical Research Trust (R.S.). J.C. is a Leukemia and Lymphoma Society (LLS) Scholar. C.H. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = feb,
doi = "10.1038/s41556-021-00835-2",
language = "English (US)",
volume = "24",
pages = "205--216",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "2",
}