Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 14, Pages 7782-7791Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1913448117
Keywords
tRNA; mRNA; modification
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Funding
- National Institute of General Medical Sciences of the National Institutes of Health [R35GM133721]
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The posttranscriptional modification of messenger RNA (mRNA) and transfer RNA (tRNA) provides an additional layer of regulatory complexity during gene expression. Here, we show that a tRNA methyltransferase, TRMT10A, interacts with an mRNA demethylase FTO (ALKBH9), both in vitro and inside cells. TRMT10A installs N-1-methylguanosine (m(1)G) in tRNA, and FTO performs demethylation on N-6-methyladenosine (m(6)A) and N-6,2'-O-dimethyladenosine (m(6)A(m)) in mRNA. We show that TRMT10A ablation not only leads to decreased m(1)G in tRNA but also significantly increases m(6)A levels in mRNA. Cross-linking and immunoprecipitation, followed by high-throughput sequencing results show that TRMT10A shares a significant overlap of associated mRNAs with FTO, and these mRNAs have accelerated decay rates potentially through the regulation by a specific m(6)A reader, YTHDF2. Furthermore, transcripts with increased m(6)A upon TRMT10A ablation contain an overrepresentation of m(1)G9-containing tRNAs codons read by tRNA(Gln(TTG)), tRNA(Arg(CCG)), and tRNA(Thr(CGT)). These findings collectively reveal the presence of coordinated mRNA and tRNA methylations and demonstrate a mechanism for regulating gene expression through the interactions between mRNA and tRNA modifying enzymes.
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