title: Structure of human RNase L reveals the basis for regulated RNA decay in the IFN response.
abstract: One of the hallmark mechanisms activated by type I interferons (IFNs) in human tissues involves cleavage of intracellular RNA by the kinase homology endoribonuclease RNase L. We report 2.8 and 2.1 angstrom crystal structures of human RNase L in complexes with synthetic and natural ligands and a fragment of an RNA substrate. RNase L forms a crossed homodimer stabilized by ankyrin (ANK) and kinase homology (KH) domains, which positions two kinase extension nuclease (KEN) domains for asymmetric RNA recognition. One KEN protomer recognizes an identity nucleotide (U), whereas the other protomer cleaves RNA between nucleotides +1 and +2. The coordinated action of the ANK, KH, and KEN domains thereby provides regulated, sequence-specific cleavage of viral and host RNA targets by RNase L.
authors.affiliation: Department of Molecular Biology, Princeton University, 216 Schultz Laboratory, Princeton, NJ 08540, USA.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Han
authors.forename: Jesse
authors.initials: J
authors.lastname: Donovan
authors.forename: Sneha
authors.initials: S
authors.lastname: Rath
authors.forename: Gena
authors.initials: G
authors.lastname: Whitney
authors.forename: Alisha
authors.initials: A
authors.lastname: Chitrakar
authors.forename: Alexei
authors.initials: A
authors.lastname: Korennykh
mesh_terms: D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology / Q000502:physiology*; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D059367:RNA Cleavage; D020871:RNA Stability; D012367:RNA, Viral / Q000737:chemistry
chemical_list: D007370:Interferon Type I; D012367:RNA, Viral; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease