Genetic or functional dependencies are often used by cancer cells to compensate the loss of function of one gene by the function of another gene in order to persist. By using genome-wide analyses and CRISPR technology, a group of U.S. scientists has now studied hundreds of cancer cell lines and discovered that such a genetic dependency exists between the two paralog genes MAGOH and MAGOHB. The two genes are functionally redundant and encode key components of the exon-junction complex, a multiprotein complex that is deposited on mRNA during splicing and contributes to various downstream processes like transport and stability of mRNA and nonsense-mediated decay. A deletion of the MAGOH gene often occurs due to loss of the short arm of chromosome 1 in cancer. In their study, the researchers investigated whether MAGOHB inhibition in the setting of decreased MAGOH dosage affects the survival of cancer cells by perturbing RNA splicing and RNA surveillance. Their results suggest that in genetically defined subsets of tumors, MAGOH and MAGOHB loss confers a vulnerability to cancer cells. This might inform the development of targeted therapeutic approaches in cancers with chromosome 1p deletion.

The results of this study have been published in Nature Genetics.