Publications

• Human BCDIN3D monomethylates cytoplasmic histidine transfer RNA.

  Martinez A., Yamashita S., Nagaike T., Sakaguchi Y., Suzuki T., Tomita K.

  Human RNA methyltransferase BCDIN3D is overexpressed in breast cancer cells, and is related to the tumorigenic phenotype and poor prognosis of breast cancer. Here, we show that cytoplasmic tRNAHis is the primary target of BCDIN3D in human cells. Recombinant human BCDIN3D, expressed in Escherichia ... >> More

  Human RNA methyltransferase BCDIN3D is overexpressed in breast cancer cells, and is related to the tumorigenic phenotype and poor prognosis of breast cancer. Here, we show that cytoplasmic tRNAHis is the primary target of BCDIN3D in human cells. Recombinant human BCDIN3D, expressed in Escherichia coli, monomethylates the 5΄-monophosphate of cytoplasmic tRNAHis efficiently in vitro. In BCDN3D-knockout cells, established by CRISPR/Cas9 editing, the methyl moiety at the 5΄-monophosphate of cytoplasmic tRNAHis is lost, and the exogenous expression of BCDIN3D in the knockout cells restores the modification in cytoplasmic tRNAHis. BCIDN3D recognizes the 5΄-guanosine nucleoside at position -1 (G-1) and the eight-nucleotide acceptor helix with the G-1-A73 mis-pair at the top of the acceptor stem of cytoplasmic tRNAHis, which are exceptional structural features among cytoplasmic tRNA species. While the monomethylation of the 5΄-monophosphate of cytoplasmic tRNAHis affects neither the overall aminoacylation process in vitro nor the steady-state level of cytoplasmic tRNAHisin vivo, it protects the cytoplasmic tRNAHis transcript from degradation in vitro. Thus, BCDIN3D acts as a cytoplasmic tRNAHis-specific 5΄-methylphosphate capping enzyme. The present results also suggest the possible involvement of the monomethylation of the 5΄-monophosphate of cytoplasmic tRNAHis and/or cytoplasmic tRNAHis itself in the tumorigenesis of breast cancer cells. << Less

  Nucleic Acids Res. 45:5423-5436(2017) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Human RNA methyltransferase BCDIN3D regulates microRNA processing.

  Xhemalce B., Robson S.C., Kouzarides T.

  MicroRNAs (miRNAs) regulate key biological processes and their aberrant expression may lead to cancer. The primary transcript of canonical miRNAs is sequentially cleaved by the RNase III enzymes, Drosha and Dicer, which generate 5' monophosphate ends that are important for subsequent miRNA functio ... >> More

  MicroRNAs (miRNAs) regulate key biological processes and their aberrant expression may lead to cancer. The primary transcript of canonical miRNAs is sequentially cleaved by the RNase III enzymes, Drosha and Dicer, which generate 5' monophosphate ends that are important for subsequent miRNA functions. In particular, the recognition of the 5' monophosphate of pre-miRNAs by Dicer is important for precise and effective biogenesis of miRNAs. Here, we identify a RNA-methyltransferase, BCDIN3D, that O-methylates this 5' monophosphate and negatively regulates miRNA maturation. Specifically, we show that BCDIN3D phospho-dimethylates pre-miR-145 both in vitro and in vivo and that phospho-dimethylated pre-miR-145 displays reduced processing by Dicer in vitro. Consistently, BCDIN3D depletion leads to lower pre-miR-145 and concomitantly increased mature miR-145 levels in breast cancer cells, which suppresses their tumorigenic phenotypes. Together, our results uncover a miRNA methylation pathway potentially involved in cancer that antagonizes the Dicer-dependent processing of miR-145 as well as other miRNAs. << Less

  Cell 151:278-288(2012) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Human BCDIN3D Is a Cytoplasmic tRNAHis-Specific 5'-Monophosphate Methyltransferase.

  Tomita K., Liu Y.

  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 fu ... >> More

  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<i>in vivo</i> and <i>in vitro</i>. 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 <i>in vitro</i> nor the steady state level or stability of tRNA^His<i>in vivo</i>. 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. << Less

  Front. Genet. 9:305-305(2018) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.