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

作者：Zheng Dinghai; Chen Chyi Ying A; Shyu Ann Bin^*

来源：RNA-A Publication of the RNA Society, 2011, 17(9): 1619-1634.

DOI：10.1261/rna.2789611

• P-body
• autophagy
• ubiquitin
• hnRNP
• microRNA
• translation
• mRNA turnover
• protein-protein interaction
• deadenylation
• bioinformatics
• phosphorylation

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.

• 出版日期2011-9