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On-line Access: 2023-11-14

Received: 2023-02-23

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 ORCID:

Tangliang LI

https://orcid.org/0000-0003-0671-9166

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Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.11 P.1062-1068

http://doi.org/10.1631/jzus.B2300126


Spatial expression of the nonsense-mediated mRNA decay factors UPF3A and UPF3B among mouse tissues


Author(s):  Xin MA, Yan LI, Chengyan Chen, Yanmin SHEN, Hua WANG, Tangliang LI

Affiliation(s):  State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; more

Corresponding email(s):   li.tangliang@sdu.edu.cn

Key Words:  Nonsense-mediated mRNA decay, UPF3A, UPF3B, Expression


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Xin MA, Yan LI, Chengyan Chen, Yanmin SHEN, Hua WANG, Tangliang LI. Spatial expression of the nonsense-mediated mRNA decay factors UPF3A and UPF3B among mouse tissues[J]. Journal of Zhejiang University Science B, 2023, 24(11): 1062-1068.

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publisher="Zhejiang University Press & Springer",
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Abstract: 
nonsense-mediated mRNA decay (NMD) is a highly conserved post-transcriptional gene regulatory mechanism in eukaryotes (Lykke-Andersen and Jensen, 2015; Kurosaki et al., 2019; Yi et al., 2021; Karousis and Mühlemann, 2022; Mailliot et al., 2022). NMD is considered as an RNA surveillance machinery to regulate mRNA abundance and eventual protein expression. NMD can recognize and degrade aberrant mRNAs, which contain premature termination codons (PTCs) located at least 50‍‒‍55 nucleotides upstream of the last exon‍‒‍exon junction. This process prevents possible toxic effects from translated truncated proteins (Lykke-Andersen and Jensen, 2015; Kurosaki et al., 2019; Karousis and Mühlemann, 2022; Mailliot et al., 2022). Previous research has shown that NMD can recognize special structures of mRNAs with physiological functions, such as the long 3' untranslated region (3' UTR) and upstream open reading frames of mRNAs, to regulate cell fate (Li et al., 2015). Thus, NMD is essential for embryonic development and tissue homeostasis in mammals (Lykke-Andersen and Jensen, 2015; Hug et al., 2016; Han et al., 2018; Jaffrey and Wilkinson, 2018; Nasif et al., 2018; Popp and Maquat, 2018; Fang et al., 2022).

无义介导的mRNA降解通路因子UPF3A和UPF3B在小鼠组织中的空间表达谱

马馨1,李岩1,陈呈燕1,申燕敏1,王哗2,李唐亮1,2
1山东大学微生物技术国家重点实验室,中国青岛市,266237
2杭州师范大学基础医学院, 浙江省衰老与癌变生物学重点实验室,中国杭州市,311121
摘要:无义介导的信使RNA(mRNA)降解途径(nonsense-mediated mRNA decay,简称为NMD)是真核生物细胞内一种重要的基因转录后表达调控机制,它积极参与一系列细胞生理和生化过程,控制细胞命运和生命体的组织稳态。NMD的缺陷会导致人类疾病,如神经发育障碍、肿瘤发生和自身免疫疾病等。UPF3(Up-frameshift protein 3)是一个核心的NMD因子,它最早在酵母中被发现。UPF3A和UPF3B是UPF3在生物进化到脊椎动物阶段出现的两个旁系同源物,在NMD中具有激活或抑制的作用。以往研究发现,UPF3B蛋白几乎在所有哺乳动物器官中均有表达,而UPF3A蛋白在除睾丸外的大多数哺乳动物组织中难以被检测到。解释这一现象的假说为:在NMD途径中,UPF3B具有比UPF3A更高的竞争性结合UPF2的能力,UPF3B和UPF2的结合促使UPF3A成为游离状态,而游离的UPF3A蛋白不稳定且易被降解。此假说提示UPF3A和UPF3B在NMD中存在拮抗作用。在本研究中,我们重新定量评估了UPF3A和UPF3B在野生型成年雄性和雌性小鼠的9个主要组织和生殖器官中的mRNA和蛋白表达,结果证实UPF3A在雄性生殖细胞中表达量最高。令人惊讶的是,我们发现在包括大脑和胸腺在内的大多数组织中,UPF3A与UPF3B的蛋白水平相当,而在小鼠脾、肺组织中,UPF3A表达高于UPF3B。公共基因表达数据进一步支持了上述发现。因此,我们的研究表明了UPF3A是小鼠组织中普遍表达的NMD因子。同时,该研究结果推测:在生理条件下,UPF3A和UPF3B蛋白之间不存在竞争抑制,且UPF3A在多种哺乳动物组织的稳态中发挥重要作用。

关键词:无义介导的mRNA降解途径(NMD);UPF3A;UPF3B

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