Unraveling regulation and new components of human P-bodies through a protein interaction framework and experimental validation

Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston, Texas 77021, USA.
RNA (Impact Factor: 4.94). 09/2011; 17(9):1619-34. DOI: 10.1261/rna.2789611
Source: PubMed


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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Available from: Dinghai Zheng, Sep 03, 2015
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    • "VCS contains two protein–protein interaction WD40 motifs, although they are not necessary to the interaction with DCP1 and DCP2. Deletion of WD40 repeats in Ge-1, the human homolog of VCS, did not compromised the localization into PB, then, WD40 repeats probably function in the recruitment of another mediators of decapping (Yu et al., 2005). The Arabidopsis DCP5 is required for decapping and repression of translation in vivo (Xu and Chua, 2009). "
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