Published on May 5, 2016 in Mol Cell volume 62(3).

PubMed ID: 27117702

DOI: S1097-2765(16)30004-1

Abstract:

METTL3 is an RNA methyltransferase implicated in mRNA biogenesis, decay, andtranslation control through N(6)-methyladenosine (m(6)A) modification. Here we findthat METTL3 promotes translation of certain mRNAs including epidermal growth factorreceptor (EGFR) and the Hippo pathway effector TAZ in human cancer cells. Incontrast to current models that invoke m(6)A reader proteins downstream of nuclearMETTL3, we find METTL3 associates with ribosomes and promotes translation in thecytoplasm. METTL3 depletion inhibits translation, and both wild-type andcatalytically inactive METTL3 promote translation when tethered to a reporter mRNA.Mechanistically, METTL3 enhances mRNA translation through an interaction with thetranslation initiation machinery. METTL3 expression is elevated in lungadenocarcinoma and using both loss- and gain-of-function studies, we find thatMETTL3 promotes growth, survival, and invasion of human lung cancer cells. Ourresults uncover an important role of METTL3 in promoting translation of oncogenes inhuman lung cancer.CI - Copyright © 2016 Elsevier Inc. All rights reserved.