文章基本信息

标题：Coordination of mRNA and tRNA methylations by TRMT10A
本地全文：下载
作者：R. Jordan Ontiveros ; Hui Shen ; Julian Stoute 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：14
页码：7782-7791
DOI：10.1073/pnas.1913448117
出版社：The National Academy of Sciences of the United States of America
摘要：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 (m¹G) in tRNA, and FTO performs demethylation on N ⁶-methyladenosine (m⁶A) and N ⁶,2′- O -dimethyladenosine (m⁶A_m) in mRNA. We show that TRMT10A ablation not only leads to decreased m¹G in tRNA but also significantly increases m⁶A 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 m⁶A reader, YTHDF2. Furthermore, transcripts with increased m⁶A upon TRMT10A ablation contain an overrepresentation of m¹G9-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.
关键词：tRNA ; mRNA ; modification