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Søren Kragh Moestrup

Activation of 2'-5' oligoadenylate synthetase by single-stranded and double-stranded RNA aptamers.

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  • Department of Molecular Biology
  • Department of Molecular Biology
  • Faculty of Science
  • Department of Medical Biochemistry
A number of small RNA molecules that are high affinity ligands for the 46-kDa form of human 2'-5' oligoadenylate synthetase have been identified by the SELEX method. Surface plasmon resonance analysis indicates that these RNAs bind to the enzyme with dissociation constants in the nanomolar range. Competition experiments indicate that the binding site for the small RNAs on the 2'-5' oligoadenylate synthetase molecule at least partially overlaps that for the synthetic double-stranded RNA, poly(I).poly(C). Several of the RNAs function as potent activators of 2'-5' oligoadenylate synthetase in vitro, although there is no correlation between binding affinity and ability to activate. The RNA aptamers having the strongest activation potential appear to have few base-paired regions. This suggests that 2'-5' oligoadenylate synthetase, which has previously been believed to be activated only by double-stranded RNA, can also be activated by RNA ligands with little secondary structure. Since 2'-5' oligoadenylate synthetase possesses no homology to other known RNA-binding proteins, the development of small specific ligands by SELEX should facilitate studies of RNA-protein interactions and may reveal novel features of the structure-function relationships involving this enzyme.
Udgivelsesdato: 1998-Feb-6
Original languageEnglish
JournalJournal of Biological Chemistry
Volume273
Issue6
Pages (from-to)3236-46
Number of pages10
ISSN0021-9258
Publication statusPublished - 1998

    Research areas

  • 2',5'-Oligoadenylate Synthetase, Base Sequence, Cell Line, Consensus Sequence, Enzyme Activation, Humans, Ligands, Molecular Sequence Data, Nucleic Acid Conformation, RNA, RNA, Double-Stranded

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