A5056272260- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Enzyme Structure and Function
- Hybrid Renewable Energy Systems
- Escherichia coli research studies
- Mitochondrial Function and Pathology
- Genomics and Phylogenetic Studies
- Cholesterol and Lipid Metabolism
The University of Tokyo
2016-2024
Abstract Mitochondria generate most cellular energy via oxidative phosphorylation. Twenty-two species of mitochondrial (mt-)tRNAs encoded in mtDNA translate essential subunits the respiratory chain complexes. mt-tRNAs contain post-transcriptional modifications introduced by nuclear-encoded tRNA-modifying enzymes. They are required for deciphering genetic code accurately, as well stabilizing tRNA. Loss tRNA frequently results severe pathological consequences. Here, we perform a comprehensive...
The mitochondrial ribosome, which translates all DNA (mtDNA)-encoded proteins, should be tightly regulated pre- and post-transcriptionally. Recently, we found RNA-DNA differences (RDDs) at human 16S (large) rRNA position 947 that were indicative of post-transcriptional modification. Here, show these RDDs result from a 1-methyladenosine (m1A) modification introduced by TRMT61B, thus being the first vertebrate methyltransferase modifies both tRNA rRNAs. m1A947 is conserved in humans...
Abstract In Caenorhabditis elegans, the N6-methyladenosine (m6A) modification by METT10, at 3'-splice sites in S-adenosyl-l-methionine (SAM) synthetase (sams) precursor mRNA (pre-mRNA), inhibits sams pre-mRNA splicing, promotes alternative splicing coupled with nonsense-mediated decay of pre-mRNAs, and thereby maintains cellular SAM level. Here, we present structural functional analyses C. elegans METT10. The structure N-terminal methyltransferase domain METT10 is homologous to that human...
MicroRNA-122 (miR-122) is highly expressed in hepatocytes, where it plays an important role regulating cholesterol and fatty acid metabolism, also a host factor required for hepatitis C virus replication. miR-122 selectively stabilized by 3' adenylation mediated the cytoplasmic poly(A) polymerase GLD-2 (also known as PAPD4 or TENT2). However, unclear how specifically stabilizes miR-122. Here, we show that QKI7 KH domain-containing RNA binding (QKI-7), one of three isoforms QKI proteins,...
Mycobacterium tuberculosis transfer RNA (tRNA) terminal nucleotidyltransferase toxin, MenT3, incorporates nucleotides at the 3'-CCA end of tRNAs, blocking their aminoacylation and inhibiting protein synthesis. Here, we show that MenT3 most effectively adds CMPs to tRNA. The crystal structure in complex with CTP reveals a CTP-specific nucleotide-binding pocket. 4-NH2 N3 O2 atoms cytosine form hydrogen bonds main-chain carbonyl oxygen P120 side chain R238, respectively. expression Escherichia...
Bacterial toxin-antitoxin modules contribute to the stress adaptation, persistence, and dormancy of bacteria for survival under environmental stresses are involved in bacterial pathogenesis. In Salmonella Typhimurium, Gcn5-related N-acetyltransferase toxin TacT reportedly acetylates α-amino groups aminoacyl moieties several aminoacyl-tRNAs, inhibits protein synthesis, promotes persister formation during infection macrophages. Here, we show that exclusively Gly-tRNAGly vivo vitro. The crystal...
Abstract Toxin-antitoxin systems in bacteria contribute to stress adaptation, dormancy, and persistence. AtaT, a type-II toxin enterohemorrhagic E. coli , reportedly acetylates the α-amino group of aminoacyl-moiety initiator Met-tRNAf Met thus inhibiting translation initiation. Here, we show that AtaT has broader specificity for aminoacyl-tRNAs than initially claimed. efficiently Gly-tRNA Gly Trp-tRNA Trp Tyr-tRNA Tyr Phe-tRNA Phe isoacceptors, addition inhibits global translation. interacts...
Escherichia coli ItaT toxin reportedly acetylates the α-amino group of aminoacyl-moiety Ile-tRNAIle specifically, using acetyl-CoA as an acetyl donor, thereby inhibiting protein synthesis. The mechanism substrate specificity had remained elusive. Here, we present functional and structural analyses E. ItaT, which revealed recognition specific aminoacyl-tRNAs for acetylation. In addition to Ile-tRNAIle, charged with hydrophobic residues, such Val-tRNAVal Met-tRNAMet, were acetylated by in...
Abstract Contact-dependent growth inhibition is a mechanism of interbacterial competition mediated by delivery the C-terminal toxin domain CdiA protein (CdiA–CT) into neighboring bacteria. The CdiA–CT enterohemorrhagic Escherichia coli EC869 (CdiA–CTEC869) cleaves 3′-acceptor regions specific tRNAs in reaction that requires translation factors Tu/Ts and GTP. Here, we show CdiA–CTEC869 has an intrinsic ability to recognize sequence substrate tRNAs, Tu:Ts complex promotes tRNA cleavage...
Abstract Contact-dependent growth inhibition (CDI) is a bacterial competition mechanism, wherein the C-terminal toxin domain of CdiA protein (CdiA-CT) transferred from one bacterium to another, impeding recipient. In uropathogenic Escherichia coli 536, CdiA-CT (CdiA-CTEC536) tRNA anticodon endonuclease that requires cysteine biogenesis factor, CysK, for its activity. However, mechanism underlying recognition and cleavage by CdiA-CTEC536 remains unresolved. Here, we present cryo-EM structure...