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开放阅读框之外:通过3'非翻译区和启动子序列对核糖体蛋白S7/真核生物核糖体蛋白S7信使核糖核酸进行旁系同源物特异性调控。

Beyond the ORF: Paralog-specific regulation of RPS7/eS7 mRNAs via 3'-UTRs and promoter sequences.

作者信息

Hayashi Sachiko, Yoshihisa Tohru

机构信息

Graduate School of Science, University of Hyogo, Ako-gun, Japan.

出版信息

PLoS One. 2025 May 30;20(5):e0324525. doi: 10.1371/journal.pone.0324525. eCollection 2025.

DOI:10.1371/journal.pone.0324525
PMID:40445952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12124516/
Abstract

In a classical view, each paralogous ribosomal protein (RP) is equally synthesized and integrated into the ribosome. Therefore, RP-paralog mRNAs are generally believed to be similarly regulated on their transcription and/or stability. In this paper, we report that two Rps7p/eS7 paralogs of Saccharomyces cerevisiae are differently regulated; deletion of RPS7A upregulates RPS7B paralogous mRNA expression but not vice versa. Their 3'-UTR sequences critically regulated the stabilities of both RPS7A and RPS7B mRNAs. Alterations in these sequences led to a diminished expression of RPS7A and RPS7B mRNAs in a transcript-dependent manner, suggesting that RPS7-paralog mRNAs have different properties for their expression and/or stability. The C-terminal tagging of the ORF and mutation analyses in the 3'-UTR indicate that both RPS7-paralog mRNAs critically rely on their 3'-UTRs for mRNA expressions and/or stabilities. We also found that activities of both RPS7A and RPS7B promoters are regulated by abundance of Rps7Ap and that Fhl1p, a key transcriptional regulator of RP genes, is essential for transcription of RPS7B but not RPS7A while simultaneous deletion of a consensus sequence for Fhl1p in the RPS7A promoter region and the FHL1 gene completely abolishes the promoter activity. These results indicate that yeast has a distinct buffering system for Rps7p production between the two RPS7-paralogs, which is sensitive to variation on their 3'-UTRs and is partially mediated in a transcription-dependent manner.

摘要

在传统观点中,每个旁系同源核糖体蛋白(RP)均以相同的方式合成并整合到核糖体中。因此,人们普遍认为RP旁系同源mRNA在转录和/或稳定性方面受到类似的调控。在本文中,我们报道酿酒酵母的两个Rps7p/eS7旁系同源物受到不同的调控;RPS7A的缺失会上调RPS7B旁系同源mRNA的表达,反之则不然。它们的3'-UTR序列对RPS7A和RPS7B mRNA的稳定性起关键调控作用。这些序列的改变导致RPS7A和RPS7B mRNA的表达以转录本依赖的方式减少,这表明RPS7旁系同源mRNA在表达和/或稳定性方面具有不同的特性。对开放阅读框(ORF)进行C端标记以及在3'-UTR中进行突变分析表明,两个RPS7旁系同源mRNA在mRNA表达和/或稳定性方面都严重依赖其3'-UTR。我们还发现,RPS7A和RPS7B启动子的活性均受Rps7Ap丰度的调控,并且Fhl1p(RP基因的关键转录调节因子)对RPS7B的转录至关重要,但对RPS7A的转录并非如此,而同时缺失RPS7A启动子区域中Fhl1p的共有序列和FHL1基因会完全消除启动子活性。这些结果表明,酵母在两个RPS7旁系同源物之间具有独特的Rps7p产生缓冲系统,该系统对其3'-UTR的变化敏感,并且部分以转录依赖的方式介导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/80832ac68e07/pone.0324525.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/6fd5b86668a3/pone.0324525.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/31b9754b1bef/pone.0324525.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/64fdeb6203cb/pone.0324525.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/3cd21cd657e1/pone.0324525.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/80832ac68e07/pone.0324525.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/6fd5b86668a3/pone.0324525.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/31b9754b1bef/pone.0324525.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/64fdeb6203cb/pone.0324525.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/3cd21cd657e1/pone.0324525.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b936/12124516/80832ac68e07/pone.0324525.g005.jpg

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本文引用的文献

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PLoS One. 2024 May 16;19(5):e0292152. doi: 10.1371/journal.pone.0292152. eCollection 2024.
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Splice-site variant in the RPS7 5'-UTR leads to a decrease in the mRNA level and development of Diamond-Blackfan anemia.RPS7 5'-UTR 中的剪接位点变异导致 mRNA 水平降低,并引发 Diamond-Blackfan 贫血。
Clin Genet. 2023 Jan;103(1):93-96. doi: 10.1111/cge.14221. Epub 2022 Sep 12.
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Duplicated ribosomal protein paralogs promote alternative translation and drug resistance.
核糖体蛋白重复基因促进选择性翻译和药物抗性。
Nat Commun. 2022 Aug 23;13(1):4938. doi: 10.1038/s41467-022-32717-y.
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Identification of novel proteins and mRNAs differentially bound to the Leishmania Poly(A) Binding Proteins reveals a direct association between PABP1, the RNA-binding protein RBP23 and mRNAs encoding ribosomal proteins.鉴定新型蛋白质和差异结合到利什曼原虫多聚(A)结合蛋白的 mRNAs,揭示了 PABP1(一种 RNA 结合蛋白)与编码核糖体蛋白的 mRNAs 之间的直接关联。
PLoS Negl Trop Dis. 2021 Oct 27;15(10):e0009899. doi: 10.1371/journal.pntd.0009899. eCollection 2021 Oct.
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Transcriptional control of ribosome biogenesis in yeast: links to growth and stress signals.酵母核糖体生物发生的转录控制:与生长和应激信号的联系。
Biochem Soc Trans. 2021 Aug 27;49(4):1589-1599. doi: 10.1042/BST20201136.
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