The mRNA decapping enzyme of Trypanosoma brucei is a promising drug target

Abstract text

Degradation of mRNAs is essential in all eukaryotes and contributes to the regulation of gene expression. The process usually starts with the removal of the poly(A) tail, is followed by the removal of the 5´ cap by a decapping complex and finishes by 5´-3´exoribonucleolytic decay. Kinetoplastids have conserved enzymes for the first and third reaction, but lack orthologues to all proteins of the decapping complex found in opisthokonts and plants. Instead, the Kinetoplastida decapping complex consists of the ApaH like phosphatase ALPH1 and several mostly Kinetoplastida-unique proteins: an example of convergent evolution.

ALPH1 is a promising drug target: it is essential in Kinetoplastida, the entire enzyme family of ApaH like phosphatases does not exist in mammals and the enzyme can be purified in an active and soluble form. Here, we present the development of a high throughput enzyme assay that we will use to screen a variety of available drug libraries.