During co-evolution with their hosts, bacterial pathogens have evolved an impressive variety of strategies to take control of cellular pathways and avoid host defence mechanisms in order to establish a productive infection. Among the range of tools dedicated to host manipulation, pathogenic intracellular bacteria employ effector proteins that are secreted into the host cytoplasm during infection. These bacterial effectors localize to specific cellular compartments where they exert their function, mostly by modifying eukaryotic proteins, reshaping cellular organelles or hijacking signaling pathways. Over the last decade, several mechanisms of action have been described for secreted bacterial effectors ranging from innate immune suppression, evasion from autophagy, apoptosis inhibition, subversion of membrane trafficking, and manipulation of cytoskeleton dynamics. However, the majority of virulence factors described to date have been shown to target eukaryotic proteins. In contrast, direct targeting of host nucleic acids remains poorly explored and mainly focused on host DNA. Although RNA targeting would offer a bacterium a wide spectrum of host processes to manipulate for its own benefit, bacterial effectors able to target RNA have not been reported. L. monocytogenes is a clinically important, food-borne human pathogen that can lead to serious sepsis, encephalitis or meningitis in immunocompromised individuals and to abortion in pregnant women. To be virulent, L. monocytogenes uses an arsenal of virulence factors that are able to subvert several host cell activities. We have recently identified Zea, the first secreted bacterial RNA-binding protein (RBP) that regulates L. monocytogenes virulence. Zea binds secreted L. monocytogenes RNA and stimulates the the type-I interferon response during infection. Zea localizes to the nucleus during infection and is found enriched at the nuclear speckles, the sites where the splicing machinery accumulates. Immunoprecipitation experiments revealed that Zea binds splicing factors in an RNA-dependent manner. We have also identified another L. monocytogenes secreted effectors, LntB, that is able to bind splicing factors and possibly host RNA. These results indicate that, by secreting RBPs, Listeria can potentially target mammalian RNA and affect RNA fate for its own benefit Our research program intends to identify the RNA targets of both Zea and LntB, characterize their interaction with the splicing factors and determine the functional role of this binding in the context of L. monocytogenes pathogenesis. Finally, by applying the interactome capture method, we plan to identify novel secreted RNA-binding effectors in L. monocytogenes. This project will pinpoint a still-uncharacterized strategy used by a bacterial pathogens to subvert its host that is via the secretion of RNA-binding effectors. We anticipate our findings to have a great impact in several research fields comprising infection biology, basic microbiology and fundamental cell biology.