SecA2 Associates with Translating Ribosomes and Contributes to the Secretion of Potent IFN-β Inducing RNAs

Abstract

Protein secretion plays a central role in modulating interactions of the human pathogen Listeria monocytogenes with its environment. Recently, secretion of RNA has emerged as an important strategy used by the pathogen to manipulate the host cell response to its advantage. In general, the Sec-dependent translocation pathway is a major route for protein secretion in L. monocytogenes, but mechanistic insights into the secretion of RNA by these pathways are lacking. Apart from the classical SecA1 secretion pathway, L. monocytogenes also encodes for a SecA paralogue (SecA2) which targets the export of a specific subset of proteins, some of which are involved in virulence. Here, we demonstrated that SecA2 co-sediments with translating ribosomes and provided evidence that it associates with a subset of secreted small non-coding RNAs (sRNAs) that induce high levels of IFN-β response in host cells. We found that enolase, which is translocated by a SecA2-dependent mechanism, binds to several sRNAs, suggesting a pathway by which sRNAs are targeted to the supernatant of L. monocytogenes.

A New Paradigm in Cancer Treatment: Identifying and Targeting Clonal Mutations

“…The second option for a Gram-positive vector at least, like L. monocytogenes, is that Eno or Zea could perhaps be programmed to bind and thus enable secretion of custom RNA molecules like the Craspase gRNA [74,75].…”

Mycobacterium tuberculosis SecA2-dependent activation of host Rig-I/MAVs signaling is not conserved in Mycobacterium marinum

“…While originally characterized for their ability to interfere with viral replication, type I interferons are increasingly recognized as important contributors in host-pathogen interactions involving intracellular bacteria. Studies in Francisella tularensis [1][2][3][4], Salmonella enterica serovar Typhimurium [5][6][7], Listeria monocytogenes [8,9] and Mycobacterium tuberculosis [10,11] have shown that these bacteria can specifically induce host type I interferons and that induction of this signaling pathway can directly impact host:bacteria interactions in vivo. For example, multiple studies have demonstrated that patients with active tuberculosis disease have blood transcriptomic signatures dominated by an upregulation of type I interferon inducible genes, including interferon-β (IFN-β).…”

Mycobacterium tuberculosisSecA2-dependent activation of host Rig-I/MAVs signaling is not conserved inMycobacterium marinum

“…While originally characterized for their ability to interfere with viral replication, type I interferons are increasingly recognized as important contributors in host-pathogen interactions involving intracellular bacteria. Studies in Francisella tularensis (1)(2)(3)(4), Salmonella enterica serovar Typhimurium (5)(6)(7), Listeria monocytogenes (8,9) and Mycobacterium tuberculosis (10,11) have shown that these bacteria can specifically induce host type I interferons and that induction of this signaling pathway can directly impact host:bacteria interactions in vivo. For example, multiple studies have demonstrated that patients with active tuberculosis disease have blood transcriptomic signatures dominated by an upregulation of type I interferon inducible genes, including interferon-ꞵ (IFN-ꞵ).…”