Abstract
Many pathogenic bacteria utilize specialized secretion systems to deliver proteins called effectors into eukaryotic cells for manipulation of host pathways. The vast majority of known effector targets are host proteins, whereas a potential targeting of host nucleic acids remains little explored. There is only one family of effectors known to target DNA directly, and effectors binding host RNA are unknown. Here, we take a two-pronged approach to search for RNA-binding effectors, combining biocomputational prediction of RNA-binding domains (RBDs) in a newly assembled comprehensive dataset of bacterial secreted proteins, and experimental screening for RNA binding in mammalian cells. Only a small subset of effectors were predicted to carry an RBD, indicating that if RNA targeting was common, it would likely involve new types of RBDs. Our experimental evaluation of effectors with predicted RBDs further argues for a general paucity of RNA binding activities amongst bacterial effectors. We obtained evidence that PipB2 and Lpg2844, effector proteins of Salmonella and Legionella species, respectively, may harbor novel biochemical activities. Our study presenting the first systematic evaluation of the RNA-targeting potential of bacterial effectors offers a basis for discussion of whether or not host RNA is a prominent target of secreted bacterial proteins.
Highlights
Many bacterial pathogens depend on virulence factors, translocated into the host by specialized secretion systems, to subvert distinct cellular functions
We obtained a non-redundant dataset of 1,022 unique proteins corresponding to one representative genus for each of 35 animal and plant bacterial pathogens or symbionts; except for Pseudomonas for which two representative genera for each of the plant and animal pathogens were included because of their distinct repertoire of effectors (Supplementary Tables S1 and S2)
In addition to the gene names and protein sequences of effectors, available data on function, localization, homology, and other features were assembled resulting in an ample resource summarizing findings on bacterial effector proteins and their functions (Supplementary Table S2)
Summary
Many bacterial pathogens depend on virulence factors, translocated into the host by specialized secretion systems, to subvert distinct cellular functions The number of these secreted proteins, known as effectors, encoded by a pathogen varies greatly from one to several hundred depending on the species[1]. It was conceivable that some bacterial effectors possess RNA-binding domains (RBDs), which would allow them to selectively target coding and non-coding RNAs to modulate host gene expression, to viral encoded RNA-binding proteins[16,17,18]. The Pfam database contains ~800 RBDs including RNA-binding protein families[23] This rich collection of domains lends itself as a reference set for the prediction of potential RNA-binding effectors
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