title: Unraveling regulation and new components of human P-bodies through a protein interaction framework and experimental validation.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston, Texas 77021, USA.
authors.forename: Dinghai
authors.initials: D
authors.lastname: Zheng
authors.forename: Chyi-Ying A
authors.initials: CY
authors.lastname: Chen
authors.forename: Ann-Bin
authors.initials: AB
authors.lastname: Shyu
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019295:Computational Biology; D022083:Cytoplasmic Structures; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques / Q000379:methods; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: D048948:14-3-3 Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering