PMID- 32678884
OWN - NLM
STAT- MEDLINE
DCOM- 20200916
LR  - 20200916
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 48
IP  - 13
DP  - 2020 Jul 27
TI  - Human OAS1 activation is highly dependent on both RNA sequence and context of 
      activating RNA motifs.
PG  - 7520-7531
LID - 10.1093/nar/gkaa513 [doi]
AB  - 2'-5'-Oligoadenylate synthetases (OAS) are innate immune sensors of cytosolic 
      double-stranded RNA (dsRNA) and play a critical role in limiting viral infection. 
      dsRNA binding induces allosteric structural changes in OAS1 that reorganize its 
      catalytic center to promote synthesis of 2'-5'-oligoadenylate and thus activation 
      of endoribonuclease L. Specific RNA sequences and structural motifs can also 
      enhance activation of OAS1 through currently undefined mechanisms. To better 
      understand these drivers of OAS activation, we tested the impact of defined 
      sequence changes within a short dsRNA that strongly activates OAS1. Both in vitro 
      and in human A549 cells, appending a 3'-end single-stranded pyrimidine (3'-ssPy) 
      can strongly enhance OAS1 activation or have no effect depending on its location, 
      suggesting that other dsRNA features are necessary for correct presentation of 
      the motif to OAS1. Consistent with this idea, we also find that the dsRNA binding 
      position is dictated by an established consensus sequence (WWN9WG). Unexpectedly, 
      however, not all sequences fitting this consensus activate OAS1 equivalently, 
      with strong dependence on the identity of both partially conserved (W) and 
      non-conserved (N9) residues. A picture thus emerges in which both specific RNA 
      features and the context in which they are presented dictate the ability of short 
      dsRNAs to activate OAS1.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Schwartz, Samantha L
AU  - Schwartz SL
AD  - Department of Biochemistry, Emory University School of Medicine, 1510 Clifton 
      Road NE, Atlanta, GA 30322, USA.
AD  - Graduate Program in Biochemistry, Cell and Developmental Biology, Graduate 
      Division of Biological and Biomedical Sciences, Emory University, USA.
FAU - Park, Esther N
AU  - Park EN
AD  - Department of Biochemistry, Emory University School of Medicine, 1510 Clifton 
      Road NE, Atlanta, GA 30322, USA.
FAU - Vachon, Virginia K
AU  - Vachon VK
AD  - Department of Biochemistry, Emory University School of Medicine, 1510 Clifton 
      Road NE, Atlanta, GA 30322, USA.
AD  - Graduate Program in Microbiology and Molecular Genetics, Graduate Division of 
      Biological and Biomedical Sciences, Emory University, USA.
FAU - Danzy, Shamika
AU  - Danzy S
AD  - Department of Microbiology and Immunology, Emory University School of Medicine, 
      1510 Clifton Road NE, Atlanta, GA 30322, USA.
FAU - Lowen, Anice C
AU  - Lowen AC
AD  - Graduate Program in Microbiology and Molecular Genetics, Graduate Division of 
      Biological and Biomedical Sciences, Emory University, USA.
AD  - Department of Microbiology and Immunology, Emory University School of Medicine, 
      1510 Clifton Road NE, Atlanta, GA 30322, USA.
FAU - Conn, Graeme L
AU  - Conn GL
AD  - Department of Biochemistry, Emory University School of Medicine, 1510 Clifton 
      Road NE, Atlanta, GA 30322, USA.
AD  - Graduate Program in Biochemistry, Cell and Developmental Biology, Graduate 
      Division of Biological and Biomedical Sciences, Emory University, USA.
AD  - Graduate Program in Microbiology and Molecular Genetics, Graduate Division of 
      Biological and Biomedical Sciences, Emory University, USA.
LA  - eng
GR  - F31 AI133950/AI/NIAID NIH HHS/United States
GR  - R01 AI144067/AI/NIAID NIH HHS/United States
GR  - T32 GM008367/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.7.- (OAS1 protein, human)
RN  - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase)
SB  - IM
MH  - 2',5'-Oligoadenylate Synthetase/chemistry/*metabolism
MH  - A549 Cells
MH  - Allosteric Regulation
MH  - Allosteric Site
MH  - Catalytic Domain
MH  - *Consensus Sequence
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Protein Binding
MH  - RNA/*chemistry/metabolism
PMC - PMC7367156
EDAT- 2020/07/18 06:00
MHDA- 2020/09/17 06:00
PMCR- 2020/06/17
CRDT- 2020/07/18 06:00
PHST- 2020/06/04 00:00 [accepted]
PHST- 2020/06/01 00:00 [revised]
PHST- 2020/03/29 00:00 [received]
PHST- 2020/07/18 06:00 [entrez]
PHST- 2020/07/18 06:00 [pubmed]
PHST- 2020/09/17 06:00 [medline]
PHST- 2020/06/17 00:00 [pmc-release]
AID - 5858452 [pii]
AID - gkaa513 [pii]
AID - 10.1093/nar/gkaa513 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2020 Jul 27;48(13):7520-7531. doi: 10.1093/nar/gkaa513.