Unraveling regulation and new components of human P-bodies through a protein interaction framework and experimental validation |
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Authors: | Zheng Dinghai Chen Chyi-Ying A Shyu Ann-Bin |
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Institution: | Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston, Texas 77021, USA. |
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Abstract: | The cellular factors involved in mRNA degradation and translation repression can aggregate into cytoplasmic domains known as GW bodies or mRNA processing bodies (P-bodies). However, current understanding of P-bodies, especially the regulatory aspect, remains relatively fragmentary. To provide a framework for studying the mechanisms and regulation of P-body formation, maintenance, and disassembly, we compiled a list of P-body proteins found in various species and further grouped both reported and predicted human P-body proteins according to their functions. By analyzing protein-protein interactions of human P-body components, we found that many P-body proteins form complex interaction networks with each other and with other cellular proteins that are not recognized as P-body components. The observation suggests that these other cellular proteins may play important roles in regulating P-body dynamics and functions. We further used siRNA-mediated gene knockdown and immunofluorescence microscopy to demonstrate the validity of our in silico analyses. Our combined approach identifies new P-body components and suggests that protein ubiquitination and protein phosphorylation involving 14-3-3 proteins may play critical roles for post-translational modifications of P-body components in regulating P-body dynamics. Our analyses provide not only a global view of human P-body components and their physical interactions but also a wealth of hypotheses to help guide future research on the regulation and function of human P-bodies. |
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Keywords: | P-body autophagy ubiquitin hnRNP microRNA translation mRNA turnover protein–protein interaction deadenylation bioinformatics phosphorylation |
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