翻译起始和 RNA 尿嘧啶酰化在多能干细胞中内源性逆转录病毒表达和神经分化中的关键作用。
Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells.
机构信息
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
出版信息
Cell Rep. 2020 Jun 2;31(9):107715. doi: 10.1016/j.celrep.2020.107715.
Abstract
Previous studies have suggested that the loss of the translation initiation factor eIF4G1 homolog NAT1 induces excessive self-renewability of naive pluripotent stem cells (PSCs); yet the role of NAT1 in the self-renewal and differentiation of primed PSCs is still unclear. Here, we generate a conditional knockout of NAT1 in primed PSCs and use the cells for the functional analyses of NAT1. Our results show that NAT1 is required for the self-renewal and neural differentiation of primed PSCs. In contrast, NAT1 deficiency in naive pluripotency attenuates the differentiation to all cell types. We also find that NAT1 is involved in efficient protein expression of an RNA uridyltransferase, TUT7. TUT7 is involved in the neural differentiation of primed PSCs via the regulation of human endogenous retrovirus accumulation. These data demonstrate the essential roles of NAT1 and TUT7 in the precise transition of stem cell fate.
摘要
先前的研究表明，翻译起始因子 eIF4G1 同源物 NAT1 的缺失会诱导原始多能干细胞（PSCs）过度自我更新；然而，NAT1 在已分化的 PSCs 自我更新和分化中的作用尚不清楚。在这里，我们在已分化的 PSCs 中生成了 NAT1 的条件敲除，并使用这些细胞进行 NAT1 的功能分析。我们的结果表明，NAT1 对于已分化的 PSCs 的自我更新和神经分化是必需的。相比之下，原始多能性中 NAT1 的缺失会减弱向所有细胞类型的分化。我们还发现，NAT1 参与 RNA 尿嘧啶转移酶 TUT7 的有效蛋白表达。TUT7 通过调节人类内源性逆转录病毒的积累参与已分化的 PSCs 的神经分化。这些数据表明 NAT1 和 TUT7 在干细胞命运的精确转变中起着重要作用。
相似文献
1
Critical Roles of Translation Initiation and RNA Uridylation in Endogenous Retroviral Expression and Neural Differentiation in Pluripotent Stem Cells.翻译起始和 RNA 尿嘧啶酰化在多能干细胞中内源性逆转录病毒表达和神经分化中的关键作用。
Cell Rep. 2020 Jun 2;31(9):107715. doi: 10.1016/j.celrep.2020.107715.
2
Long noncoding RNA CCDC144NL-AS1 knockdown induces naïve-like state conversion of human pluripotent stem cells.长链非编码 RNA CCDC144NL-AS1 敲低诱导人多能干细胞向原始态样转换。
Stem Cell Res Ther. 2019 Jul 29;10(1):220. doi: 10.1186/s13287-019-1323-9.
3
Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.Nat1促进特定蛋白质的翻译，这些蛋白质可诱导小鼠胚胎干细胞分化。
Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):340-345. doi: 10.1073/pnas.1617234114. Epub 2016 Dec 21.
4
RNAi-mediated knock-down of arylamine N-acetyltransferase-1 expression induces E-cadherin up-regulation and cell-cell contact growth inhibition.RNAi 介导的芳香胺 N-乙酰基转移酶-1 表达敲低诱导 E-钙黏蛋白上调和细胞-细胞接触生长抑制。
PLoS One. 2011 Feb 9;6(2):e17031. doi: 10.1371/journal.pone.0017031.
5
Genetic and small molecule inhibition of arylamine N-acetyltransferase 1 reduces anchorage-independent growth in human breast cancer cell line MDA-MB-231.遗传和小分子抑制芳香胺 N-乙酰基转移酶 1 降低人乳腺癌细胞系 MDA-MB-231 的无锚定依赖性生长。
Mol Carcinog. 2018 Apr;57(4):549-558. doi: 10.1002/mc.22779. Epub 2018 Feb 3.
6
Arylamine -Acetyltransferase 1 Regulates Expression of Matrix Metalloproteinase 9 in Breast Cancer Cells: Role of Hypoxia-Inducible Factor 1-.芳基胺乙酰基转移酶 1 通过调节缺氧诱导因子 1-调控乳腺癌细胞中基质金属蛋白酶 9 的表达。
Mol Pharmacol. 2019 Nov;96(5):573-579. doi: 10.1124/mol.119.117432. Epub 2019 Aug 23.
7
Effect of arylamine acetyltransferase Nat3 gene knockout on N-acetylation in the mouse.芳胺乙酰基转移酶Nat3基因敲除对小鼠N-乙酰化作用的影响。
Drug Metab Dispos. 2007 Jul;35(7):1064-70. doi: 10.1124/dmd.107.015396. Epub 2007 Apr 2.
8
Arylamine N-acetyltransferase 1 protects against reactive oxygen species during glucose starvation: Role in the regulation of p53 stability.芳香胺 N-乙酰基转移酶 1 在葡萄糖饥饿期间保护细胞免受活性氧的侵害：在调节 p53 稳定性中的作用。
PLoS One. 2018 Mar 8;13(3):e0193560. doi: 10.1371/journal.pone.0193560. eCollection 2018.
9
Small-Molecule Induction of Canine Embryonic Stem Cells Toward Naïve Pluripotency.小分子诱导犬胚胎干细胞向原始多能性转变
Stem Cells Dev. 2016 Aug 15;25(16):1208-22. doi: 10.1089/scd.2016.0103. Epub 2016 Jul 28.
10
N-acetyltransferase ARD1-NAT1 regulates neuronal dendritic development.N-乙酰转移酶ARD1-NAT1调节神经元树突发育。
Genes Cells. 2008 Nov;13(11):1171-83. doi: 10.1111/j.1365-2443.2008.01235.x.
引用本文的文献
1
Co-option of an endogenous retrovirus (LTR7-HERVH) in early human embryogenesis: becoming useful and going unnoticed.内源性逆转录病毒（LTR7-HERVH）在人类早期胚胎发育中的适应性利用：发挥作用且未被察觉。
Mob DNA. 2025 Jul 5;16(1):27. doi: 10.1186/s13100-025-00361-0.
2
EIF3D safeguards the homeostasis of key signaling pathways in human primed pluripotency.真核起始因子3D（EIF3D）维持人类原始多能性中关键信号通路的稳态。
Sci Adv. 2025 Apr 11;11(15):eadq5484. doi: 10.1126/sciadv.adq5484. Epub 2025 Apr 9.
3
Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.逆转录转座子：从神经发育和衰老角度洞察神经疾病
Transl Neurodegener. 2025 Mar 25;14(1):14. doi: 10.1186/s40035-025-00471-y.
4
SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA.SARS-CoV-2 Nsp1 与起始因子 EIF1 和 1A 合作，选择性地增强病毒 RNA 的翻译。
PLoS Pathog. 2024 Feb 9;20(2):e1011535. doi: 10.1371/journal.ppat.1011535. eCollection 2024 Feb.
5
Neurogenesis in primates versus rodents and the value of non-human primate models.灵长类动物与啮齿动物的神经发生以及非人灵长类动物模型的价值。
Natl Sci Rev. 2023 Sep 15;10(11):nwad248. doi: 10.1093/nsr/nwad248. eCollection 2023 Nov.
6
HERVs and Cancer-A Comprehensive Review of the Relationship of Human Endogenous Retroviruses and Human Cancers.人类内源性逆转录病毒与癌症——人类内源性逆转录病毒与人类癌症关系的全面综述
Biomedicines. 2023 Mar 17;11(3):936. doi: 10.3390/biomedicines11030936.
7
Eukaryotic translation initiation factor eIF4G2 opens novel paths for protein synthesis in development, apoptosis and cell differentiation.真核翻译起始因子 eIF4G2 在发育、细胞凋亡和细胞分化过程中为蛋白质合成开辟了新的途径。
Cell Prolif. 2023 Mar;56(3):e13367. doi: 10.1111/cpr.13367. Epub 2022 Dec 22.
8
Exocyst complex component 2 is a potential host factor for SARS-CoV-2 infection.外排体复合物成分2是严重急性呼吸综合征冠状病毒2感染的潜在宿主因子。
iScience. 2022 Nov 18;25(11):105427. doi: 10.1016/j.isci.2022.105427. Epub 2022 Oct 22.
9
Multi-omics approach reveals posttranscriptionally regulated genes are essential for human pluripotent stem cells.多组学方法揭示转录后调控基因对人类多能干细胞至关重要。
iScience. 2022 Apr 25;25(5):104289. doi: 10.1016/j.isci.2022.104289. eCollection 2022 May 20.
10
A stress-reduced passaging technique improves the viability of human pluripotent cells.一种减轻压力的传代技术可提高人类多能细胞的活力。
Cell Rep Methods. 2022 Jan 24;2(2):100155. doi: 10.1016/j.crmeth.2021.100155. eCollection 2022 Feb 28.
本文引用的文献
1
The Pediatric Cell Atlas: Defining the Growth Phase of Human Development at Single-Cell Resolution.儿科细胞图谱：以单细胞分辨率定义人类发育的生长阶段。
Dev Cell. 2019 Apr 8;49(1):10-29. doi: 10.1016/j.devcel.2019.03.001. Epub 2019 Mar 28.
2
A widespread alternate form of cap-dependent mRNA translation initiation.一种广泛存在的帽依赖性 mRNA 翻译起始的替代形式。
Nat Commun. 2018 Aug 3;9(1):3068. doi: 10.1038/s41467-018-05539-0.
3
MYC Releases Early Reprogrammed Human Cells from Proliferation Pause via Retinoblastoma Protein Inhibition.MYC 通过抑制视网膜母细胞瘤蛋白使早期重编程的人类细胞从增殖暂停中释放出来。
Cell Rep. 2018 Apr 10;23(2):361-375. doi: 10.1016/j.celrep.2018.03.057.
4
A pathology atlas of the human cancer transcriptome.人类癌症转录组病理学图谱。
Science. 2017 Aug 18;357(6352). doi: 10.1126/science.aan2507.
5
Transcriptome-wide measurement of translation by ribosome profiling.核糖体图谱法进行的转录组范围的翻译测量。
Methods. 2017 Aug 15;126:112-129. doi: 10.1016/j.ymeth.2017.05.028. Epub 2017 Jun 1.
6
A subcellular map of the human proteome.人类蛋白质组的亚细胞图谱。
Science. 2017 May 26;356(6340). doi: 10.1126/science.aal3321. Epub 2017 May 11.
7
Extensive translation of circular RNAs driven by N-methyladenosine.由N-甲基腺苷驱动的环状RNA的广泛翻译。
Cell Res. 2017 May;27(5):626-641. doi: 10.1038/cr.2017.31. Epub 2017 Mar 10.
8
Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.Nat1促进特定蛋白质的翻译，这些蛋白质可诱导小鼠胚胎干细胞分化。
Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):340-345. doi: 10.1073/pnas.1617234114. Epub 2016 Dec 21.
9
Autotaxin-mediated lipid signaling intersects with LIF and BMP signaling to promote the naive pluripotency transcription factor program.自分泌运动因子介导的脂质信号传导与白血病抑制因子（LIF）和骨形态发生蛋白（BMP）信号传导相互作用，以促进原始多能性转录因子程序。
Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12478-12483. doi: 10.1073/pnas.1608564113. Epub 2016 Oct 13.
10
Cap-independent translation by DAP5 controls cell fate decisions in human embryonic stem cells.DAP5介导的不依赖帽结构的翻译调控人类胚胎干细胞的细胞命运决定。
Genes Dev. 2016 Sep 1;30(17):1991-2004. doi: 10.1101/gad.285239.116.
Zotero 插件