Browsing by Author "Shih, Jing-Wen"

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Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in stress granule assembly and stress response
(2012-01-01)
Shih, Jing-Wen
;
Wang, Wei-Ting
;
Tsai, Tsung-Yuan
;
Kuo, Chu-Yun
;
Li, Hao-Kang
Upon environmental insults, SGs (stress granules) aid cell survival by serving as sites of translational silencing. RNA helicase DDX3 was reported to associate with SGs. However, its role in SG physiology remains undefined. We have demonstrated previously that DDX3 acts as an eIF4E (eukaryotic initiation factor 4E)-inhibitory protein to suppress translation. In the present study, we indentified the SG marker PABP1 [poly(A)-binding protein 1] as another direct interaction partner of DDX3. We established various stimuli as novel stressors that direct DDX3 with eIF4E and PABP1 into SGs, but not to processing bodies. Interestingly, down-regulation of DDX3 interfered with SG assembly, led to nuclear accumulation of PABP1 and reduced cell viability following stress. Conversely, supplementation with a shRNA (short hairpin RNA)-resistant DDX3 restored SG formation, the translocation of PABP1 into SGs and cell survival. Notably, the SG-inducing capacity of DDX3 is independent of its ATPase and helicase activities, but mapped to the eIF4E-binding region. Moreover, the eIF4E-binding-defective mutant DDX3 was impaired in its SG-inducing ability and protective effect on cell survival under adverse conditions. All together, the present study has characterized DDX3 as a pivotal SG-nucleating factor and illustrates co-ordinative roles for DDX3, eIF4E and PABP1 in integrating environmental stress with translational regulation.
Human DExD/H RNA helicases: Emerging roles in stress survival regulation
(2014-09-25)
Shih, Jing-Wen
;
Lee, Yan-Hwa Wu
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交大名義發表
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生物科技學系
;
National Chiao Tung University
Environmental stresses threatening cell homeostasis trigger various cellular responses ranging from the activation of survival pathways to eliciting programmed cell death. Cellular stress response highly depends on the nature and level of the insult as well as the cell type. Notably, the interplay among all these responses will ultimately determine the fate of the stressed cell. Human DExD/H RNA helicases are ubiquitous molecular motors rearranging RNA secondary structure in an ATP-dependent fashion. These highly conserved enzymes participate in nearly all aspects of cellular process involving RNA metabolism. Although numerous functions of DExD/H RNA helicases are well documented, their importance in stress response is only just becoming evident. This review outlines our current knowledge on major mechanistic themes of human DExD/H RNA helicases in response to stressful stimuli, especially on emerging molecular models for the functional roles of these enzymes in the stress survival regulation. (C) 2014 The Authors. Published by Elsevier B.V.