title: The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response.
abstract: The interferon (IFN)-regulated endoribonuclease RNase-L is involved in multiple aspects of the antimicrobial innate immune response. It is the terminal component of an RNA cleavage pathway in which dsRNA induces the production of RNase-L-activating 2-5A by the 2'-5'-oligoadenylate synthetase. The active nuclease then cleaves ssRNAs, both cellular and viral, leading to downregulation of their expression and the generation of small RNAs capable of activating retinoic acid-inducible gene-I (RIG-I)-like receptors or the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome. This leads to IFNβ expression and IL-1β activation respectively, in addition to broader effects on immune cell function. RNase-L is also one of a growing number of innate immune components that interact with the cell cytoskeleton. It can bind to several cytoskeletal proteins, including filamin A, an actin-binding protein that collaborates with RNase-L to maintain the cellular barrier to viral entry. This antiviral activity is independent of catalytic function, a unique mechanism for RNase-L. We also describe here the interaction of RNase-L with the E3 ubiquitin ligase and scaffolding protein, ligand of nump protein X (LNX), a regulator of tight junction proteins. In order to better understand the significance and context of these novel binding partners in the antimicrobial response, other innate immune protein interactions with the cytoskeleton are also discussed.
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. hezelle@som.umaryland.edu.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. hezelle@som.umaryland.edu.|Research Services, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, USA. hezelle@som.umaryland.edu.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ezelle
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA. Malathi.Krishnamurthy@utoledo.edu.
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Malathi
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. bhassel@som.umaryland.edu.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. bhassel@som.umaryland.edu.
authors.forename: Bret A
authors.initials: BA
authors.lastname: Hassel
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000201:enzymology / Q000276:immunology*; D003599:Cytoskeleton / Q000276:immunology* / Q000382:microbiology*; D004722:Endoribonucleases / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D014777:Virus Diseases / Q000201:enzymology / Q000276:immunology*; D014780:Viruses / Q000276:immunology
chemical_list: D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease
keywords: LNX; RNase-L; actin; cytoskeleton; filamin A; inflammasome; innate immunity; interferon