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甲藻中丰富的 mRNA mA 修饰:基因调控的新层次。

Abundant mRNA mA modification in dinoflagellates: a new layer of gene regulation.

机构信息

Department of Human Cell Biology and Genetics, Joint Laboratory of Guangdong & Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen, 518000, China.

The First Affiliated Hospital of Zhengzhou University & Institute of Reproductive Health, Henan Academy of Innovations in Medical Science, Zhengzhou, 450000, China.

出版信息

EMBO Rep. 2024 Nov;25(11):4655-4673. doi: 10.1038/s44319-024-00234-2. Epub 2024 Sep 2.

DOI:10.1038/s44319-024-00234-2
PMID:39223385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11549093/
Abstract

Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (mA) remain controversial due to its limited presence in typical eukaryotic mRNA. This study provides a comprehensive map of mA in dinoflagellate mRNA and shows that mA, rather than N6-methyladenosine (mA), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetric distribution along mature transcripts. In Amphidinium carterae, we identify 6549 mA sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many of which are involved in regulating carbon and nitrogen metabolism. Enriched within 3'UTRs, dinoflagellate mRNA mA levels negatively correlate with translation efficiency. Nitrogen depletion further decreases mRNA mA levels. Our data suggest that distinctive patterns of mA modification might influence the expression of metabolism-related genes through translational control.

摘要

甲藻是一类单细胞真核浮游植物,表现出最小的转录调控,代表了探索基因表达的独特模型。由于其在典型真核 mRNA 中的有限存在,mRNA N1-甲基腺苷(mA)的生物合成、分布、调控和功能仍然存在争议。本研究提供了甲藻 mRNA 中 mA 的全面图谱,并表明 mA(而不是 mA)是各种甲藻物种中最普遍的成熟转录本内部 mRNA 修饰,在成熟转录本中呈不对称分布。在 Amphidinium carterae 中,我们在 3196 个基因的转录本中识别出 6549 个 mA 位点,这些位点的特征是具有非 tRNA T 环样序列基序,其中许多基因参与调节碳氮代谢。富含 3'UTRs 的甲藻 mRNA mA 水平与翻译效率呈负相关。氮的消耗进一步降低了 mRNA mA 的水平。我们的数据表明,独特的 mA 修饰模式可能通过翻译控制影响与代谢相关的基因的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/66e3bb550276/44319_2024_234_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/92af620ac0e4/44319_2024_234_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/a692403ecd63/44319_2024_234_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/375185a29da9/44319_2024_234_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/c2e2590203d4/44319_2024_234_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/b1c74aa99718/44319_2024_234_Fig5_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/8ca91d3559a1/44319_2024_234_Fig6_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/c6a8b5149ace/44319_2024_234_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/05b7553854e7/44319_2024_234_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/66e3bb550276/44319_2024_234_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/92af620ac0e4/44319_2024_234_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/a692403ecd63/44319_2024_234_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/375185a29da9/44319_2024_234_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/c2e2590203d4/44319_2024_234_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/b1c74aa99718/44319_2024_234_Fig5_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/8ca91d3559a1/44319_2024_234_Fig6_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/c6a8b5149ace/44319_2024_234_Fig7_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/05b7553854e7/44319_2024_234_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0dc/11549093/66e3bb550276/44319_2024_234_Fig9_ESM.jpg

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本文引用的文献

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NAR Genom Bioinform. 2024 Feb 10;6(1):lqae016. doi: 10.1093/nargab/lqae016. eCollection 2024 Mar.
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mA in CAG repeat RNA binds to TDP-43 and induces neurodegeneration.CAG 重复扩增的 mA 与 TDP-43 结合并诱导神经退行性变。
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协调翻译专门每天三次调节甲藻新陈代谢。
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