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一种tRNA修饰有助于在细胞内实现最佳生长。

A tRNA modification in facilitates optimal intracellular growth.

作者信息

Tomasi Francesca G, Kimura Satoshi, Rubin Eric J, Waldor Matthew K

机构信息

Department of Immunology and Infectious Diseases Harvard T. H. Chan School of Public Health, Boston, MA USA.

Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.

出版信息

bioRxiv. 2023 Jun 9:2023.02.20.529267. doi: 10.1101/2023.02.20.529267.

DOI:10.1101/2023.02.20.529267
PMID:36865327
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9979996/
Abstract

Diverse chemical modifications fine-tune the function and metabolism of tRNA. Although tRNA modification is universal in all kingdoms of life, profiles of modifications, their functions, and physiological roles have not been elucidated in most organisms including the human pathogen, ( ), the causative agent of tuberculosis. To identify physiologically important modifications, we surveyed the tRNA of , using tRNA sequencing (tRNA-seq) and genome-mining. Homology searches identified 23 candidate tRNA modifying enzymes that are predicted to create 16 tRNA modifications across all tRNA species. Reverse transcription-derived error signatures in tRNA-seq predicted the sites and presence of 9 modifications. Several chemical treatments prior to tRNA-seq expanded the number of predictable modifications. Deletion of genes encoding two modifying enzymes, TruB and MnmA, eliminated their respective tRNA modifications, validating the presence of modified sites in tRNA species. Furthermore, the absence of attenuated growth in macrophages, suggesting that MnmA-dependent tRNA uridine sulfation contributes to intracellular growth. Our results lay the foundation for unveiling the roles of tRNA modifications in pathogenesis and developing new therapeutics against tuberculosis.

摘要

多种化学修饰可微调转运RNA（tRNA）的功能和代谢。尽管tRNA修饰在所有生命王国中都很普遍，但在包括人类病原体结核分枝杆菌（ ）（结核病的病原体）在内的大多数生物体中，修饰的概况、其功能和生理作用尚未阐明。为了鉴定具有生理重要性的修饰，我们使用tRNA测序（tRNA-seq）和基因组挖掘技术对结核分枝杆菌的tRNA进行了研究。同源性搜索鉴定出23种候选tRNA修饰酶，预计这些酶可在所有tRNA种类中产生16种tRNA修饰。tRNA-seq中逆转录衍生的错误特征预测了9种修饰的位点和存在情况。在tRNA-seq之前进行的几种化学处理增加了可预测修饰的数量。删除编码两种修饰酶TruB和MnmA 的基因消除了它们各自的tRNA修饰，证实了tRNA种类中修饰位点的存在。此外，MnmA的缺失减弱了结核分枝杆菌在巨噬细胞中的生长，这表明依赖MnmA的tRNA尿苷硫酸化有助于结核分枝杆菌的细胞内生长。我们的结果为揭示tRNA修饰在结核分枝杆菌发病机制中的作用以及开发抗结核病新疗法奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/f5835652336d/nihpp-2023.02.20.529267v2-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/0792376c0072/nihpp-2023.02.20.529267v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/e1f0da18f59c/nihpp-2023.02.20.529267v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/9e4c5812c80d/nihpp-2023.02.20.529267v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/bc5b2cc0e67d/nihpp-2023.02.20.529267v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/cef172c73b96/nihpp-2023.02.20.529267v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/ffe05ef70801/nihpp-2023.02.20.529267v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/f5835652336d/nihpp-2023.02.20.529267v2-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/0792376c0072/nihpp-2023.02.20.529267v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/e1f0da18f59c/nihpp-2023.02.20.529267v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/9e4c5812c80d/nihpp-2023.02.20.529267v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/bc5b2cc0e67d/nihpp-2023.02.20.529267v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/cef172c73b96/nihpp-2023.02.20.529267v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/ffe05ef70801/nihpp-2023.02.20.529267v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46af/10257868/f5835652336d/nihpp-2023.02.20.529267v2-f0007.jpg

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本文引用的文献

1
Identification of a novel 5-aminomethyl-2-thiouridine methyltransferase in tRNA modification.鉴定 tRNA 修饰中的新型 5-氨基甲基-2-硫尿嘧啶甲基转移酶。
Nucleic Acids Res. 2023 Feb 28;51(4):1971-1983. doi: 10.1093/nar/gkad048.
2
The tRNA identity landscape for aminoacylation and beyond.tRNA 识别景观：氨酰化及其他功能
Nucleic Acids Res. 2023 Feb 28;51(4):1528-1570. doi: 10.1093/nar/gkad007.
3
UniProt: the Universal Protein Knowledgebase in 2023.UniProt：2023 年的通用蛋白质知识库。
Nucleic Acids Res. 2023 Jan 6;51(D1):D523-D531. doi: 10.1093/nar/gkac1052.
4
Quantitative sequencing using BID-seq uncovers abundant pseudouridines in mammalian mRNA at base resolution.BID-seq 定量测序技术在碱基分辨率水平上揭示了哺乳动物 mRNA 中的大量假尿嘧啶核苷。
Nat Biotechnol. 2023 Mar;41(3):344-354. doi: 10.1038/s41587-022-01505-w. Epub 2022 Oct 27.
5
tRNA methylation resolves codon usage bias at the limit of cell viability.tRNA 甲基化可解决细胞存活极限时的密码子使用偏好性问题。
Cell Rep. 2022 Oct 25;41(4):111539. doi: 10.1016/j.celrep.2022.111539.
6
Sequential action of a tRNA base editor in conversion of cytidine to pseudouridine.tRNA 碱基编辑器连续作用将胞嘧啶转化为假尿嘧啶。
Nat Commun. 2022 Oct 11;13(1):5994. doi: 10.1038/s41467-022-33714-x.
7
tRNA-mA modification promotes T cell expansion via efficient MYC protein synthesis.tRNA-mA 修饰通过高效的 MYC 蛋白合成促进 T 细胞扩增。
Nat Immunol. 2022 Oct;23(10):1433-1444. doi: 10.1038/s41590-022-01301-3. Epub 2022 Sep 22.
8
Mitochondrial RNA modifications shape metabolic plasticity in metastasis.线粒体 RNA 修饰塑造转移中的代谢可塑性。
Nature. 2022 Jul;607(7919):593-603. doi: 10.1038/s41586-022-04898-5. Epub 2022 Jun 29.
9
tRNA dysregulation and disease.tRNA 失调与疾病。
Nat Rev Genet. 2022 Nov;23(11):651-664. doi: 10.1038/s41576-022-00501-9. Epub 2022 Jun 9.
10
Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA.转录组范围的映射揭示了包括 mRNA 在内的多样化二氢尿嘧啶图谱。
PLoS Biol. 2022 May 24;20(5):e3001622. doi: 10.1371/journal.pbio.3001622. eCollection 2022 May.