METTL3 promotes translation in human cancer cells

By Shuibin Lin, Junho Choe, P. Du, Robinson Triboulet, Richard I. Gregory. Molecules and Cells, 2016

1,283 citations recorded by the source corpus.

METTL3 is a RNA methyltransferase implicated in mRNA biogenesis, decay, and translation control through N6-methyladenosine (m6A) modification. Here we find that METTL3 promotes translation of certain mRNAs including epidermal growth factor receptor (EGFR) and the Hippo pathway effector TAZ in human cancer cells. In contrast to current models that invoke m6A reader proteins downstream of nuclear METTL3, we find METTL3 associates with ribosomes and promotes translation in the cytoplasm. METTL3 depletion inhibits translation, and both wild-type and catalytically inactive METTL3 promote translation when tethered to a reporter mRNA. Mechanistically, METTL3 enhances mRNA translation through an interaction with the translation initiation machinery. METTL3 expression is elevated in lung adenocarcinoma and using both loss- and gain-of-function studies we find that METTL3 promotes growth, survival, and invasion of human lung cancer cells. Our results uncover an important role of METTL3 in promoting translation of oncogenes in human lung cancer.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1be2381bfc16d634e8b4320b14ea534f8c59cda9

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In Molecular Biology

1. Chuan He
2. Hailing Shi
3. Jiangbo W
4. Syuzo Kaneko
5. Masaaki Komatsu
6. Ken Asada
7. Ken Takasawa
8. Jianjun Chen

Citations in the corpus

• YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs (2017, background): “Additional roles in m(6)A-based regulation of cap-independent translation have been described for eIF3 as well as for the catalytic methyltransferase component METTL3, each functioning to promote the translation of methylated mRNAs (Lin et al., 2016; Meyer et al., 2015).”
• m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells (2017, methodology): “The METTL3 catalytic mutant (aa395-398, DPPW/APPA)- expressing lentiviral vector was prepared by sub-cloning the mutant human METTL3 sequences from pFLAG-CMV2-METTL3 (mutant) vector (Lin et al., 2016) into the CSC lentiviral vector.”
• Critical Roles of N6-Methyladenosine (m6A) in Cancer and Virus Infection (2020, background): “Another study showed that METTL3 knockdown, along with YTHDF2 deficiency, increases the RNA stability of the d2 isoform of vacuolar ATPase V0 domain (ATP6V0D2), and prolongs its half-life, indicating the impact of m6A in regulation of RNA stability [63].”