Structure of human RNase L reveals the basis for regulated RNA decay in the IFN response.

TitleStructure of human RNase L reveals the basis for regulated RNA decay in the IFN response.
Publication TypeJournal Article
Year of Publication2014
AuthorsHan, Y, Donovan, J, Rath, S, Whitney, G, Chitrakar, A, Korennykh, A
JournalScience
Volume343
Issue6176
Pagination1244-8
Date Published2014 Mar 14
ISSN1095-9203
KeywordsCrystallography, X-Ray, Endoribonucleases, HeLa Cells, Hepatitis B virus, Humans, Interferon Type I, Protein Multimerization, Protein Structure, Tertiary, RNA Cleavage, RNA Stability, RNA, Viral
Abstract

<p>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.</p>

DOI10.1126/science.1249845
Alternate JournalScience
PubMed ID24578532
PubMed Central IDPMC4731867
Grant ListP41 GM111244 / GM / NIGMS NIH HHS / United States
R01 GM110161 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States