METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis

Rui Su, Lei Dong, Yangchan Li, Min Gao, P. Cody He, Wei Liu, Jiangbo Wei, Zhicong Zhao, Lei Gao, Li Han, Xiaolan Deng, Chenying Li, Emily Prince, Brandon Tan, Ying Qing, Xi Qin, Chao Shen, Meilin Xue, Keren Zhou, Zhenhua ChenJianhuang 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

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)205-216
Number of pages12
JournalNature cell biology
Volume24
Issue number2
DOIs
StatePublished - Feb 2022

ASJC Scopus subject areas

  • Cell Biology

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