Rearrangement of a 1,3-trans-[Pt(NH3)2[(GXG)-N7G,N7G]] intrastrand cross-link into interstrand cross-links within RNA duplexes

Nucleic Acids Res. 2002 Dec 1;30(23):5222-8. doi: 10.1093/nar/gkf672.

Abstract

The cross-linking reaction described previously in the DNA and 2'-O-methyl RNA series is extended to RNA duplexes. A 17mer single-stranded RNA containing the 1,3-trans-[Pt(NH3)2[(GAG)-N7G,N7G]] intrastrand chelate, named G*AG* (* indicating a platinated base) gives, upon pairing with the complementary RNA strand, the G*AG/CUC* interstrand cross-link. The rate of the reaction in 200 mM NaClO4 is similar to that observed for DNA-RNA duplexes. It depends on the added Na+ or Mg2+ cation and on its concentration. RNA duplexes containing GA/GA or AG/AG tandem mismatches in the rearrangement triplet core were also studied. The major interstrand cross-links, G*AG/CGA* and G*AG/AGC*, are accompanied by a minor one involving the central G of the CGA or AGC complementary sequence G*AG/CG*A and G*AG/AG*C. In 200 mM NaClO4, the G*A/GA tandem mismatch does not modify the rate of the cross-linking rearrangement whereas the AG*/AG mismatch slows it down by a factor of four. Our results reflect the predominance of the local structure of the rearrangement core over the nucleophility of the cross-linking base. They also show that the reaction could be used to trap tertiary structures of naturally occurring RNAs, including those with the commonly encountered GA/GA mismatch.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing
  • Base Sequence
  • Binding Sites
  • Cross-Linking Reagents / chemistry
  • DNA Adducts / chemistry
  • Kinetics
  • Models, Genetic
  • Nucleic Acid Heteroduplexes / chemistry*
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / metabolism
  • RNA / chemistry*
  • Ribonucleotides / chemistry

Substances

  • Cross-Linking Reagents
  • DNA Adducts
  • Nucleic Acid Heteroduplexes
  • Organoplatinum Compounds
  • Ribonucleotides
  • RNA