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死后组织中与细胞死亡相关的核糖体RNA切割及其法医学应用

Cell Death-Associated Ribosomal RNA Cleavage in Postmortem Tissues and Its Forensic Applications.

作者信息

Kim Ji Yeon, Kim Yunmi, Cha Hyo Kyeong, Lim Hye Young, Kim Hyungsub, Chung Sooyoung, Hwang Juck-Joon, Park Seong Hwan, Son Gi Hoon

机构信息

Department of Legal Medicine, College of Medicine, Korea University, Seoul 02841, Korea.

Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea.

出版信息

Mol Cells. 2017 Jun 30;40(6):410-417. doi: 10.14348/molcells.2017.0039. Epub 2017 Jun 15.

Abstract

Estimation of postmortem interval (PMI) is a key issue in the field of forensic pathology. With the availability of quantitative analysis of RNA levels in postmortem tissues, several studies have assessed the postmortem degradation of constitutively expressed RNA species to estimate PMI. However, conventional RNA quantification as well as biochemical and physiological changes employed thus far have limitations related to standardization or normalization. The present study focuses on an interesting feature of the subdomains of certain RNA species, in which they are site-specifically cleaved during apoptotic cell death. We found that the D8 divergent domain of ribosomal RNA (rRNA) bearing cell death-related cleavage sites was rapidly removed during postmortem RNA degradation. In contrast to the fragile domain, the 5' terminal region of 28S rRNA was remarkably stable during the postmortem period. Importantly, the differences in the degradation rates between the two domains in mammalian 28S rRNA were highly proportional to increasing PMI with a significant linear correlation observed in mice as well as human autopsy tissues. In conclusion, we demonstrate that comparison of the degradation rates between domains of a single RNA species provides quantitative information on postmortem degradation states, which can be applied for the estimation of PMI.

摘要

死后间隔时间(PMI)的估计是法医病理学领域的一个关键问题。随着对死后组织中RNA水平进行定量分析技术的出现,一些研究评估了组成性表达的RNA种类的死后降解情况以估计PMI。然而,迄今为止所采用的传统RNA定量以及生化和生理变化在标准化或归一化方面存在局限性。本研究聚焦于某些RNA种类亚结构域的一个有趣特征,即在凋亡性细胞死亡过程中它们会发生位点特异性切割。我们发现,带有与细胞死亡相关切割位点的核糖体RNA(rRNA)的D8分歧结构域在死后RNA降解过程中会迅速被去除。与这个易降解结构域相反,28S rRNA的5'末端区域在死后期间非常稳定。重要的是,哺乳动物28S rRNA中这两个结构域之间的降解速率差异与PMI的增加高度成比例,在小鼠以及人类尸检组织中均观察到显著的线性相关性。总之,我们证明了比较单一RNA种类不同结构域之间的降解速率可提供关于死后降解状态的定量信息,这可用于PMI的估计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4e9/5523017/897a57c057e9/molce-40-6-410f1.jpg

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