In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 14 ( 2020-04-07), p. 7782-7791
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1913448117
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2020
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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