Journal
NUCLEIC ACIDS RESEARCH
Volume 45, Issue 9, Pages 5423-5436Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkx051
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Funding
- JSPS
- Ministry of Education, Science, Sports and Culture of Japan
- Takeda Science Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Hamaguchi Foundation for the Advancement of Biochemistry
- Ministry of Education, Science, Sports, and Culture of Japan
- Grants-in-Aid for Scientific Research [26220205, 26251009, 16K18510, 26113002] Funding Source: KAKEN
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Human RNA methyltransferase BCDIN3D is over-expressed in breast cancer cells, and is related to the tumorigenic phenotype and poor prognosis of breast cancer. Here, we show that cytoplasmic tRNA(His) is the primary target of BCDIN3D in human cells. Recombinant human BCDIN3D, expressed in Escherichia coli, monomethylates the 5'-monophosphate of cytoplasmic tRNA(His) efficiently in vitro. In BCDN3D-knockout cells, established by CRISPR/Cas9 editing, the methyl moiety at the 5'-monophosphate of cytoplasmic tRNA(His) is lost, and the exogenous expression of BCDIN3D in the knockout cells restores the modification in cytoplasmic tRNA(His). BCIDN3D recognizes the 5'-guanosine nucleoside at position - 1 (G(-1)) and the eight-nucleotide acceptor helix with the G(-1)-A(73) mis-pair at the top of the acceptor stem of cytoplasmic tRNA(His), which are exceptional structural features among cytoplasmic tRNA species. While the monomethylation of the 5'-monophosphate of cytoplasmic tRNA(His) affects neither the overall aminoacylation process in vitro nor the steady-state level of cytoplasmic tRNA(His) in vivo, it protects the cytoplasmic tRNA(His) transcript from degradation in vitro. Thus, BCDIN3D acts as a cytoplasmic tRNA(His)-specific 5'-methylphosphate capping enzyme. The present results also suggest the possible involvement of the monomethylation of the 5'-monophosphate of cytoplasmic tRNA(His) and/or cytoplasmic tRNA(His) itself in the tumorigenesis of breast cancer cells.
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