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人肾细胞发育过程中转录 RNA 衍生片段的特征:Dicer 在 tRF 生物发生中的作用。

Characteristics of Transfer RNA-Derived Fragments Expressed during Human Renal Cell Development: The Role of Dicer in tRF Biogenesis.

机构信息

Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznań, Poland.

出版信息

Int J Mol Sci. 2022 Mar 26;23(7):3644. doi: 10.3390/ijms23073644.

Abstract

tRNA-derived fragments participate in the regulation of many processes, such as gene silencing, splicing and translation in many organisms, ranging from bacteria to humans. We were interested to know how tRF abundance changes during the different stages of renal cell development. The research model used here consisted of the following human renal cells: hESCs, HEK-293T, HK-2 and A-489 kidney tumor cells, which, together, mimic the different stages of kidney development. The characteristics of the most abundant tRFs, tRFGly(CCC), tRFVal(AAC) and tRFArg(CCU), were presented. It was found that these parental tRNAs present in cells are the source of many tRFs, thus increasing the pool of potential regulatory RNAs. Indeed, a bioinformatic analysis showed the possibility that tRFGly(CCC) and tRRFVal(AAC) could regulate the activity of a range of kidney proteins. Moreover, the distribution of tRFs and the efficiency of their expression is similar in adult and embryonic stem cells. During the formation of tRFs, HK-2 cells resemble A-498 cancer cells more than other cells. Additionally, we postulate the involvement of Dicer nuclease in the formation of tRF-5b in all the analyzed tRNAs. To confirm this, 293T NoDice cells, which in the absence of Dicer activity do not generate tRF-5b, were used.

摘要

tRNA 衍生片段参与许多过程的调节,例如基因沉默、剪接和翻译,在从细菌到人类的许多生物中。我们有兴趣了解 tRF 丰度在肾细胞发育的不同阶段如何变化。这里使用的研究模型包括以下人类肾细胞:hESCs、HEK-293T、HK-2 和 A-489 肾肿瘤细胞,它们共同模拟了肾脏发育的不同阶段。介绍了最丰富的 tRFs(tRFGly(CCC)、tRFVal(AAC)和 tRFArg(CCU))的特征。研究发现,这些存在于细胞中的亲本 tRNA 是许多 tRF 的来源,从而增加了潜在调节 RNA 的池。实际上,生物信息学分析表明,tRFGly(CCC)和 tRRFVal(AAC)可能调节一系列肾脏蛋白的活性。此外,tRFs 的分布及其表达效率在成体和胚胎干细胞中相似。在 tRF 形成过程中,HK-2 细胞比其他细胞更类似于 A-498 癌细胞。此外,我们假设 Dicer 核酸内切酶参与了所有分析的 tRNA 中 tRF-5b 的形成。为了证实这一点,使用了缺乏 Dicer 活性的 293T NoDice 细胞,这些细胞不能产生 tRF-5b。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21e7/8998818/668bfb63e508/ijms-23-03644-g001.jpg

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