Pharmacological targeting of mRNA cap formation

Details Pharmacological targeting of mRNA cap formation Pharmacological targeting of mRNA cap formation

1998-11-09

2000-08-22

Fredman, Jeffrey

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving nucleic acid

424 946, 4352541, 536 221, 536 231, 536 243, C12Q 168, A61K 3748, C12N 119, C07H 2102

Patent

active

061070408

ABSTRACT:
This invention provides methods for the discovery of molecules that target an essential aspect of eukaryotic gene expression--the formation of the mRNA 5' cap m7GpppN. An underlying principle of this invention is the use of a different strains of a test organism that differ only in the composition or source of the essential cap-forming enzymes. The invention provides isogenic yeast strains that derive all their capping activities from fungal sources versus mammalian sources. These strains form the basis of a differential growth inhibition assay to identify molecules that specifically target the fungal capping apparatus. This invention also provides a method to screen in vitro for molecules that inhibit fungal RNA triphosphatase, an essential enzyme that catalyzes the first of three steps in cap synthesis.

REFERENCES:
Yue et al., "Mammalian capping enzyme complements mutant Saccharomyces cerevisiae lacking mRNA guanylytransferase and selectively binds the elongating form of RNA polymerase II", vol. 94, pp. 12898-12903, Nov. 1997.
Ho et al, "Genetic, Physical, and Functional Interactions between the Triphosphatase and Guanylytransferase Components of the Yeast mRNA Capping Apparatus", Molecular and Cellular Biology, vol. 18(9), pp. 5189-5198, Sep. 1998.

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