Abstract
P-bodies are dynamic aggregates of RNA and proteins involved in several post-transcriptional regulation processes. P-bodies have been shown to play important roles in regulating viral infection, whereas their interplay with bacterial pathogens, specifically intracellular bacteria that extensively manipulate host cell pathways, remains unknown. Here, we report that Salmonella infection induces P-body disassembly in a cell type-specific manner, and independently of previously characterized pathways such as inhibition of host cell RNA synthesis or microRNA-mediated gene silencing. We show that the Salmonella-induced P-body disassembly depends on the activation of the SPI-2 encoded type 3 secretion system, and that the secreted effector protein SpvB plays a major role in this process. P-body disruption is also induced by the related pathogen, Shigella flexneri, arguing that this might be a new mechanism by which intracellular bacterial pathogens subvert host cell function.
Highlights
A significant fraction of cellular messenger RNAs are not translated immediately after their export from the nucleus to the cytoplasm, being subjected to quality control and regulatory mechanisms that lead to mRNA degradation or translation repression
These different fates of transcripts have been associated with specific subcellular localizations: mRNAs being actively translated are associated with polysomes; mRNAs targeted for degradation or translation repression accumulate in P-bodies (a.k.a. mRNA processing bodies or GW bodies); and, in response to stress conditions, mRNAs stalled in translation initiation accumulate in stress granules
Bacterial pathogens are endowed with extraordinarily abilities to subvert host cell functions as they initiate and establish an infection
Summary
A significant fraction of cellular messenger RNAs are not translated immediately after their export from the nucleus to the cytoplasm, being subjected to quality control and regulatory mechanisms that lead to mRNA degradation or translation repression. These different fates of transcripts have been associated with specific subcellular localizations: mRNAs being actively translated are associated with polysomes; mRNAs targeted for degradation or translation repression accumulate in P-bodies (a.k.a. mRNA processing bodies or GW bodies); and, in response to stress conditions, mRNAs stalled in translation initiation accumulate in stress granules. PBs and SGs are often detected docked to each other, and it has been suggested that mRNAs can move between these two compartments [9]
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