한빛사 논문
Kwon Jeong1,2,†, Incheol Ryu1,2,†, Joori Park1,2,†, Hyun Jung Hwang1,2, Hongseok Ha1,2, Yeonkyoung Park1,2, Sang Taek Oh1,2 and Yoon Ki Kim1,2,*
1 Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, Republic of Korea and 2 Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea
*To whom correspondence should be addressed.
†The authors wish it to be known that, in their opinion, the first three authors should be regarded as Joint First Authors.
Abstract
Newly synthesized mRNAs are exported from the nucleus to cytoplasm with a 5′-cap structure bound by the nuclear cap-binding complex (CBC). During or after export, the CBC should be properly replaced by cytoplasmic cap-binding protein eIF4E for efficient protein synthesis. Nonetheless, little is known about how the replacement takes place. Here, we show that double-stranded RNA-binding protein staufen1 (STAU1) promotes efficient replacement by facilitating an association between the CBC–importin α complex and importin β. Our transcriptome-wide analyses and artificial tethering experiments also reveal that the replacement occurs more efficiently when an mRNA associates with STAU1. This event is inhibited by a key nonsense-mediated mRNA decay factor, UPF1, which directly interacts with STAU1. Furthermore, we find that cellular apoptosis that is induced by ionizing radiation is accompanied by inhibition of the replacement via increased association between STAU1 and hyperphosphorylated UPF1. Altogether, our data highlight the functional importance of STAU1 and UPF1 in the course of the replacement of the CBC by eIF4E, adding a previously unappreciated layer of post-transcriptional gene regulation.
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