Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNA

Acta Crystallogr D Biol Crystallogr. 2011 Feb;67(Pt 2):97-104. doi: 10.1107/S0907444910050900. Epub 2011 Jan 8.


A sequence around the start codon of the mRNA of human thymidylate synthase (TS) folds into a secondary-structure motif in which the initiation site is sequestered in a metastable hairpin. Binding of the protein to its own mRNA at the hairpin prevents the production of TS through a translation-repression feedback mechanism. Stabilization of the mRNA hairpin by other ligands has been proposed as a strategy to reduce TS levels in anticancer therapy. Rapidly proliferating cells require high TS activity to maintain the production of thymidine as a building block for DNA synthesis. The crystal structure of a model oligonucleotide (TS1) that represents the TS-binding site of the mRNA has been determined. While fluorescence studies showed that the TS1 RNA preferentially adopts a hairpin structure in solution, even at high RNA concentrations, an asymmetric dimer of two hybridized TS1 strands was obtained in the crystal. The TS1 dimer contains an unusual S-turn motif that also occurs in the `off' state of the human ribosomal decoding site RNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation*
  • RNA, Messenger / chemistry*
  • Regulatory Elements, Transcriptional*
  • Thymidylate Synthase / chemistry*


  • RNA, Messenger
  • Thymidylate Synthase

Associated data

  • PDB/3MEI