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病毒调节 N6-甲基腺苷(m6A) 机器的结构分析表明,黑蝙蝠()和埃及果蝠()在哺乳动物中具有进化保守性。

Structural Analysis of Virus Regulatory N6-Methyladenosine (m6A) Machinery of the Black Flying Fox () and the Egyptian Fruit Bat () Shows Evolutionary Conservation Amongst Mammals.

机构信息

Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YG, UK.

Department of Zoonoses, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.

出版信息

Genes (Basel). 2024 Oct 23;15(11):1361. doi: 10.3390/genes15111361.

DOI:10.3390/genes15111361
PMID:39596561
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11594476/
Abstract

BACKGROUND

N6-methyladenosine (m6A) is an abundant RNA epitranscriptomic modification in eukaryotes. The m6A machinery includes cellular writer, eraser and reader proteins that regulate m6A. () (the Australian black flying fox) and () (the Egyptian fruit bat) are bats associated with several viral zoonoses yet neglected in the field of m6A epigenetics studies.

OBJECTIVES

This study utilises various bioinformatics and in silico tools to genetically identify, characterise and annotate the m6A machinery in and .

METHODS

A range of bioinformatic tools were deployed to comprehensively characterise all known m6A-associated proteins of and Results: Phylogenetically, the m6A fat mass and obesity-associated protein (FTO) eraser placed the order Chiroptera (an order including all bat species) in a separate clade. Additionally, it showed the lowest identity matrices in and when compared to other mammals (74.1% and 72.8%) and (84.0% and 76.1%), respectively. When compared to humans, genetic loci-based analysis of and showed syntenic conservation in multiple flanking genes of 8 out the 10 m6A-associated genes. Furthermore, amino acid alignment and protein tertiary structure of the two bats' m6A machinery demonstrated conservation in the writers but not in erasers and readers, compared to humans.

CONCLUSIONS

These studies provide foundational annotation and genetic characterisation of m6A machinery in two important species of bats which can be exploited to study bat-virus interactions at the interface of epitranscriptomics.

摘要

背景

N6-甲基腺苷(m6A)是真核生物中丰富的 RNA 转录后修饰。m6A 机制包括细胞写入器、擦除器和读取器蛋白,它们调节 m6A。(澳大利亚黑飞狐)和(埃及果蝠)是与几种人畜共患病相关的蝙蝠,但在 m6A 表观遗传学研究领域被忽视。

目的

本研究利用各种生物信息学和计算工具,在 和 中从遗传学上鉴定、描述和注释 m6A 机制。

方法

使用了一系列生物信息学工具来全面描述 和 的所有已知 m6A 相关蛋白。

结果

从系统发育上看,m6A 肥胖相关脂肪组织蛋白(FTO)擦除器将包括所有蝙蝠物种的翼手目(一个目)置于一个单独的分支中。此外,与其他哺乳动物(分别为 74.1%和 72.8%)和 (分别为 84.0%和 76.1%)相比,它在 和 中的身份矩阵最低。与人类相比,基于遗传基因座的 和 分析显示,10 个 m6A 相关基因中的 8 个的侧翼基因在多个位点上具有同线性保守性。此外,与人类相比,这两种蝙蝠的 m6A 机制的氨基酸比对和蛋白质三级结构显示,在写入器中具有保守性,但在擦除器和读取器中没有保守性。

结论

这些研究为两种重要蝙蝠物种的 m6A 机制提供了基础注释和遗传特征,可以用于研究在表观转录组学界面处的蝙蝠-病毒相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/4b16cef0825d/genes-15-01361-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/600f4390118d/genes-15-01361-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/ed7770113c7f/genes-15-01361-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/c1f11c05e8c9/genes-15-01361-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/d7f09f833533/genes-15-01361-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/704c9a612eb6/genes-15-01361-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/37c51c574caf/genes-15-01361-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/4a5b4f3d9516/genes-15-01361-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/4b16cef0825d/genes-15-01361-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/600f4390118d/genes-15-01361-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/ed7770113c7f/genes-15-01361-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/c1f11c05e8c9/genes-15-01361-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/d7f09f833533/genes-15-01361-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/704c9a612eb6/genes-15-01361-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/37c51c574caf/genes-15-01361-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/4a5b4f3d9516/genes-15-01361-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf9f/11594476/4b16cef0825d/genes-15-01361-g008.jpg

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