[대학원 생명과학과 세미나 안내]
연사 : 최준호 박사 (Stem Cell Program, Boston Children's Hospital)
연제 : The m6A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells
일시 : 2016년 10월 24일 (월) 오후 3시30분
장소 : 하나과학관 A동 307호
초청교수 : 김윤기 교수
Abstract
METTL3 is an 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.