Antisense regulation of IS10 transposase synthesis is mediated by a small RNA molecule, RNA-OUT which is complementary to the 5' region of the IS10 transposase mRNA, RNA-IN. Pairing between the two species in vivo prevents initiation of RNA-IN translation by steric occlusion of the ribosome binding site. The goal of this work is to develop a mathematical basis for antisense repression in vivo. Thus, by modeling antisense pairing as a bimolecular reaction in vivo, I have developed equations which relate the degree of translation inhibition to a relative pairing rate constant, k, and the in vivo RNA-OUT concentration. Using the methodology developed here, an analysis of mutations in the first three 5' bases of RNA-IN reveals a semi-logarithmic relationship between k and ΔG, the estimated change in the free energy of pairing. Such correlations are not observed for mutations at other positions, implicating only the first three 5' bases of RNA-IN in the formation of a pairing nucleus with RNA-OUT. Finally, an analysis of mutations that affect antisense action at a post-nucleation step has been undertaken here and a specific model for how these mutations may affect antisense pairing is discussed.
ASJC Scopus subject areas
- Statistics and Probability
- Modeling and Simulation
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Agricultural and Biological Sciences(all)
- Applied Mathematics