PRMT5 and cancer: The cosubstrate SAM readily degrades into MTA,which in turn isa SAM-competitive inhibitor of PRMT5.24 Phosphorolysis of MTA, producing adenine and 5′-methylthioribose-1-phosphate,is catalyzed by MTAP and is a critical pathway for the regenerationof both adenine and methionine.25 In addition,the MTAP gene is located adjacent to the cyclin-dependent kinase inhibitor2A (CDKN2A) gene, a tumor suppressor gene that isdeleted in many forms of cancer.