METTL1/WDR4 Inhibitors

METTL1/WDR4 Interactions

METTL1 is an RNA m7G methyltransferase that complexes with WDR4, an essential protein cofactor of METTL1, to catalyze the methylation reaction of RNA m7G on tRNA. This methylation event has been found to increase rates of cancer as methylated m7G tRNA allows for greater efficiency in mRNA translation, leading to greater incidences of oncogenic RNA processing. Previous knockout studies of the METTL1 gene have shown decreased protein translation, while upregulation of METTL1 has demonstrated increased mRNA translation efficiency linked to cancer development; increased levels of methylated m7G tRNA promote the translation of oncogenic and cell cycle regulation mRNA. It is thought that inhibition of the initial METTL1/WDR4 interaction will limit m7G methylation of tRNA, thus reducing oncogenic protein proliferation. Our lab is beginning efforts to explore this interaction and discover potential small molecule inhibitors that specifically target this event.

Relevant Publications