Biochemical analysis of human tRNA(His) guanylyltransferase in mitochondrial tRNA(His) maturation

• Nakamura, Akiyoshi

• Wang, Daole

• Komatsu, Yasuo

Abstract

Mitochondria contain their own protein synthesis machinery, which includes mitochondrial tRNA maturation. It has been suggested that mammalian mitochondrial tRNA(His) (mtRNA(His)) is matured by post-transcriptional addition of guanosine at the 1 position (G(-1)), which serves as an identity element for mitochondrial histidyl-tRNA synthetase. However, the exact maturation process of mammalian mtRNA(His) remains unclear. In cytoplasmic tRNA(His) (ctRNA(His)) maturation, tRNA(His) guanylyltransferase (Thg1) adds a GTP onto the 5'-terminal of ctRNA(His) and then removes the 5'-pyrophosphate to yield the mature 5'-monophospholylated G(-1)-ctRNA(His) (pG(-1)-ctRNA(His)). Although mammalian Thg1 is localized to both the cytoplasm and mitochondria, it remains unclear whether mammalian Thg1 plays a role in mtRNA(His) maturation in mitochondria. Here, we demonstrated that human Thg1 (hThg1) catalyzes the G(-1) addition reaction for both human ctRNA(His) and mtRNA(His) through recognition of the anticodon. While hThg1 catalyzed consecutive GTP additions to mtRNA(His) in vitro, it did not exhibit any activity toward mature pG(-1)-mtRNA(His). We further found that hThg1 could add a GMP directly to the 5'-terminal of mtRNA(His) in a template-dependent manner, but fungal Thg1 could not. Therefore, we hypothesized that acceleration of the pyrophosphate removal activity before or after the G(-1) addition reaction is a key feature of hThg1 for maintaining a normal 5'-terminal of mtRNA(His) in human mitochondria. This study provided a new insight into the differences between tRNA(His) maturation in the cytoplasm and mitochondria of humans. (C) 2018 Elsevier Inc. All rights reserved.

Journal

• Biochemical and biophysical research communications

  Biochemical and biophysical research communications 503 (3), 2015-2021, 2018-09-10

  Elsevier

Keywords

• Transfer RNA
• RNA modification
• Mitochondria
• Guanylyltransferase

Details

• CRID: 1050564289017162112
• NII Article ID: 120006718707
• DOI: 10.1016/j.bbrc.2018.07.150
• HANDLE: 2115/75437
• ISSN: 0006291X
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X18316541?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0006291X18316541?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN