Human BCDIN3D Is a Cytoplasmic tRNA(His)-Specific 5′-Monophosphate Methyltransferase

Bicoid interacting 3 domain containing RNA methyltransferase (BCDIN3D) is a member of the Bin3 methyltransferase family and is evolutionary conserved from worm to human. BCDIN3D is overexpressed in breast cancer, which is associated with poor prognosis of breast cancers. However, the biological functions and properties of BCDIN3D have been enigmatic. Recent studies have revealed that human BCDIN3D monomethylates 5′-monophsosphate of cytoplasmic tRNA(His) in vivo and in vitro. BCDIN3D recognizes the unique and exceptional structural features of cytoplasmic tRNA(His) and discriminates tRNA(His) from other cytoplasmic tRNA species. Thus, BCDIN3D is a tRNA(His)-specific 5′-monophosphate methyltransferase. Methylation of the 5′-phosphate group of tRNA(His) does not significantly affect tRNA(His) aminoacylation by histidyl-tRNA synthetase in vitro nor the steady state level or stability of tRNA(His) in vivo. Hence, methylation of the 5′-phosphate group of tRNA(His) by BCDIN3D or tRNA(His) itself may be involved in certain unknown biological processes, beyond protein synthesis. This review discusses recent reports on BCDIN3D and the possible association between 5′-phosphate monomethylation of tRNA(His) and the tumorigenic phenotype of breast cancer.