人类乳腺癌中核糖体 RNA 伪苷酸化的变化

NAR Cancer Pub Date : 2023-05-30 eCollection Date: 2023-06-01 DOI:10.1093/narcan/zcad026
Chiara Barozzi, Federico Zacchini, Angelo Gianluca Corradini, Monica Morara, Margherita Serra, Veronica De Sanctis, Roberto Bertorelli, Erik Dassi, Lorenzo Montanaro
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引用次数: 0

摘要

RNA 修饰是多种生物和病理过程的关键调节因子。它们大量存在于核糖体 RNA(rRNA)上,在 mRNA 翻译过程中起到调节核糖体功能的作用。RNA 修饰途径的改变与肿瘤发生以及其他人类疾病有关。在这项研究中,我们利用 RBS-Seq 技术(包括 RNA 亚硫酸氢盐处理)和一种新的 NGS 方法,定量评估了乳腺癌样本中 rRNA 的特异位点假酸化模式。我们发现不同部位的患者之间存在很大差异。与参考 RNA 相比,肿瘤中调控最紊乱的位置出现了高修饰。至于 rRNA 修饰的 2'O- 甲基化水平,我们检测到了可变和稳定的假尿苷位点,其中最稳定的位点在进化过程中最为保守。我们还观察到,特定位点的假尿苷化水平与一些临床和生物病理肿瘤特征有关,它们能够区分不同的患者群。这项研究是新近出现的高通量位点特异性假尿嘧啶检测方法为了解人类肿瘤发生的核糖体内在变化所做贡献的第一个实例。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Alterations of ribosomal RNA pseudouridylation in human breast cancer.

Alterations of ribosomal RNA pseudouridylation in human breast cancer.

Alterations of ribosomal RNA pseudouridylation in human breast cancer.

Alterations of ribosomal RNA pseudouridylation in human breast cancer.

RNA modifications are key regulatory factors for several biological and pathological processes. They are abundantly represented on ribosomal RNA (rRNA), where they contribute to regulate ribosomal function in mRNA translation. Altered RNA modification pathways have been linked to tumorigenesis as well as to other human diseases. In this study we quantitatively evaluated the site-specific pseudouridylation pattern in rRNA in breast cancer samples exploiting the RBS-Seq technique involving RNA bisulfite treatment coupled with a new NGS approach. We found a wide variability among patients at different sites. The most dysregulated positions in tumors turned out to be hypermodified with respect to a reference RNA. As for 2'O-methylation level of rRNA modification, we detected variable and stable pseudouridine sites, with the most stable sites being the most evolutionary conserved. We also observed that pseudouridylation levels at specific sites are related to some clinical and bio-pathological tumor features and they are able to distinguish different patient clusters. This study is the first example of the contribution that newly available high-throughput approaches for site specific pseudouridine detection can provide to the understanding of the intrinsic ribosomal changes occurring in human tumors.

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