Going full circle: Validation of P-body dispersion in hepatitis C virus-infected patients

Abstract

Stability of biologically active molecules is a tightly regulated process that plays a key role in cellular homeostasis. This regulation is mediated by multiple mechanisms including the degradation of proteins by the proteasome or turnover of messenger RNAs by high-molecular-weight mRNA-protein complexes called Processing (P) bodies [1]. These are microscopically distinct aggregates of proteins and RNAs serving multiple purposes including, in addition to mRNA degradation, mRNA storage and microRNA (miRNA)-mediated suppression of mRNA translation. Degradation of mRNAs in P-bodies requires numerous enzymes such as deadenylases that remove the poly(A) tails at the 30 end of the mRNA, the Dcp enzymes removing the cap-structure at the 50 end and ribonucleases such as the exoribonuclease Xrn1, catalyzing nucleolytic degradation. This complex protein composition earned various names to these aggregates such as ‘‘Xrn1 foci’’, ‘‘DCP-bodies’’, or ‘‘GW-bodies’’, but nowadays P-bodies is a widely accepted term referring to mRNA-protein aggregates involved in mRNA turnover. Assembly of P-bodies is a dynamic process that is linked to the translation status of the cell, requiring on the one hand the presence of some ‘‘core’’ protein components such as the GW182 scaffolding proteins and on the other hand the accumulation of a large pool of untranslated mRNAs in a cell. Thus, inhibition of mRNA translation by different stresses leads to P-body accumulation. Interestingly, P-body abundance is also influenced by the cell cycle with proliferating cells containing bigger and more abundant P-bodies than quiescent cells. P-bodies are also motile structures which can, under stress conditions, dock transiently to stress granules (SGs) and exchange some components. This might be involved in the degradation of transcripts stored in SGs. Owing to their role in mRNA decay, P-bodies represent a potential threat to efficient replication of RNA viruses. Consequently, many RNA viruses such as West Nile virus, Poliovirus