| Abstract |
METTL3 is an RNA methyltransferase implicated in mRNA biogenesis, decay, and
translation control through N(6)-methyladenosine (m(6)A) 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 m(6)A 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. |
