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UPF3A 在小鼠多能性和体细胞核mRNA 非依赖降解途径中是可有可无的。

UPF3A is dispensable for nonsense-mediated mRNA decay in mouse pluripotent and somatic cells.

机构信息

State Key Laboratory of Microbial Technology, Shandong University, Qingdao, China.

Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany.

出版信息

Life Sci Alliance. 2023 Mar 30;6(6). doi: 10.26508/lsa.202201589. Print 2023 Jun.

DOI:10.26508/lsa.202201589
PMID:36997282
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10070813/
Abstract

Nonsense-mediated mRNA decay (NMD) is a highly conserved regulatory mechanism of post-transcriptional gene expression in eukaryotic cells. NMD plays essential roles in mRNA quality and quantity control and thus safeguards multiple biological processes including embryonic stem cell differentiation and organogenesis. UPF3A and UPF3B in vertebrate species, originated from a single gene in yeast, are key factors in the NMD machinery. Although UPF3B is a well-recognized weak NMD-promoting factor, whether UPF3A functions in promoting or suppressing NMD is under debate. In this study, we generated a conditional knockout mouse strain and established multiple lines of embryonic stem cells and somatic cells without UPF3A. Through extensive analysis on the expressions of 33 NMD targets, we found UPF3A neither represses NMD in mouse embryonic stem cells, somatic cells, nor in major organs including the liver, spleen, and thymus. Our study reinforces that UPF3A is dispensable for NMD when UPF3B is present. Furthermore, UPF3A may weakly and selectively promote NMD in certain murine organs.

摘要

无意义介导的 mRNA 降解（NMD）是真核细胞中转录后基因表达的一种高度保守的调控机制。NMD 在 mRNA 的质量和数量控制中发挥着重要作用，从而保障了包括胚胎干细胞分化和器官发生在内的多种生物学过程。脊椎动物物种中的 UPF3A 和 UPF3B 来源于酵母中的单个基因，是 NMD 机制中的关键因素。尽管 UPF3B 是一种公认的弱 NMD 促进因子，但 UPF3A 是否在促进或抑制 NMD 中发挥作用仍存在争议。在这项研究中，我们生成了一种条件性敲除小鼠品系，并建立了多条缺乏 UPF3A 的胚胎干细胞和体细胞系。通过对 33 个 NMD 靶标表达的广泛分析，我们发现 UPF3A 既不抑制小鼠胚胎干细胞、体细胞，也不抑制肝脏、脾脏和胸腺等主要器官中的 NMD。我们的研究进一步证实，当 UPF3B 存在时，UPF3A 对于 NMD 是可有可无的。此外，UPF3A 可能在某些特定的鼠类器官中弱且选择性地促进 NMD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/b75d88184564/LSA-2022-01589_FigS9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/5faf3b59da40/LSA-2022-01589_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/33bd28ee2038/LSA-2022-01589_FigS4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/b75d88184564/LSA-2022-01589_FigS9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/601ca1da5cf3/LSA-2022-01589_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/07e03e19678b/LSA-2022-01589_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/b966fd3fbe9e/LSA-2022-01589_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/4c735d5bc00e/LSA-2022-01589_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/5faf3b59da40/LSA-2022-01589_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/33bd28ee2038/LSA-2022-01589_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/76084b4e4816/LSA-2022-01589_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/bae19fd3bf7c/LSA-2022-01589_FigS6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/9b55404e060d/LSA-2022-01589_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/19d4c2f3258a/LSA-2022-01589_FigS7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82cf/10070813/04d8cece4619/LSA-2022-01589_FigS8.jpg
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