NAIST 奈良先端科学技術大学院大学 バイオサイエンス領域


Investigating the role of mRNA structure in regulating eukaryotic translation

演題 Investigating the role of mRNA structure in regulating eukaryotic translation
講演者 Dr. Christopher S. Fraser(Assistant Professor, Molecular and Cellular Biology, College of Biological Sciences, UC Davis)
使用言語 English
日時 2013年12月10日(火曜日) 13:30~14:30
場所 大セミナー室
Elevated levels of eukaryotic initiation factor 4E (eIF4E) frequently occur in a variety of human cancers. Consistent with this, overexpression of eIF4E promotes cellular transformation by selectively increasing the translation of proliferative and prosurvival mRNAs. These mRNAs possess highly structured 5'-UTRs that impede ribosome recruitment and scanning, yet the mechanism for how eIF4E abundance elevates their translation is not easily explained by its cap-binding activity. We now show that eIF4E possesses an unexpected second function in translation initiation by strongly stimulating eukaryotic initiation factor 4A (eIF4A) helicase activity. Importantly, we demonstrate that this activity promotes mRNA restructuring in a manner that is independent of its cap-binding function. To explain these findings, we show that the eIF4E-binding site in eukaryotic initiation factor 4G (eIF4G) functions as an autoinhibitory domain to modulate its ability to stimulate eIF4A helicase activity. Binding of eIF4E counteracts this autoinhibition, enabling eIF4G to stimulate eIF4A helicase activity. Finally, we have successfully separated the two functions of eIF4E to show that its helicase promoting activity increases the rate of translation by a mechanism that is distinct from its cap-binding function. Based on our results, we propose that maintaining a connection between eIF4E and eIF4G throughout scanning provides a plausible mechanism to explain how eIF4E abundance selectively stimulates the translation of highly structured proliferation and tumor-promoting mRNAs
問合せ先 原核生物分子遺伝学
真木 寿治 (