Immunohistochemical localization of exoribonucleases (DIS3L2 and XRN1) in intranuclear inclusion body disease
Immunohistochemical localization of exoribonucleases (DIS3L2 and XRN1) in intranuclear inclusion body disease
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DOI：
10.1016/j.neulet.2017.10.061
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发表时间：
2018-01
影响因子：
2.5
通讯作者：
F. Mori;K. Tanji;Y. Miki;Y. Toyoshima;H. Sasaki;Mari Yoshida;A. Kakita;H. Takahashi;K. Wakabayashi
中科院分区：
文献类型：
--
作者：
F. Mori;K. Tanji;Y. Miki;Y. Toyoshima;H. Sasaki;Mari Yoshida;A. Kakita;H. Takahashi;K. Wakabayashi
在衰老和神经退行性疾病的不同条件下，mRNA的转换控制着基因的表达。多聚谷氨酰胺(PolyQ)病和核内包涵体病(INIBD)是以核内包涵体形成为特征的神经退行性疾病。这些包涵体对与肌萎缩侧索硬化症相关的几种蛋白呈免疫阳性反应。在肌萎缩侧索硬化症中，RNA从基因转录到降解(RNA代谢)的处理已被报道发生了改变。我们推测，与RNA代谢相关的蛋白质也参与了多Q病和INIBD核包涵体的形成。3‘-5’外切核糖核酸酶Dis312和5‘-3’外切核糖核酸酶XRN1在mRNA衰退中起关键作用。应用免疫组织化学方法，结合抗Dis3l2和XRN1的抗体，对多发性神经元病和INIBD患者及正常对照组的脑组织进行了检测。在对照组，Dis3l2和XRN1的免疫反应分别位于神经元胞浆和神经束。在INIBD中，Dis312和XRN1的免疫反应存在于神经元和神经胶质核包涵体中。在这些包涵体中，泛素与Dis3l2或XRN1共定位。然而，在PolyQ病中，Dis312和XRN1的核包涵体免疫阴性。这些发现提示外切核糖核酸酶与核包涵体的隔离可能与INIBD的发病机制有关。
mRNA turnover controls gene expression under various conditions in aging and neurodegenerative diseases. Polyglutamine (polyQ) diseases and intranuclear inclusion body disease (INIBD) are neurodegenerative diseases characterized by the formation of nuclear inclusions. These inclusions are immunopositive for several proteins associated with amyotrophic lateral sclerosis. In amyotrophic lateral sclerosis, the processing of RNA from gene transcription through degradation (RNA metabolism) has been reported to be altered. We hypothesized that the proteins associated with RNA metabolism are also involved in the formation of nuclear inclusions in polyQ diseases and INIBD. 3′-5′ exoribonuclease DIS3L2 and 5′-3′ exoribonuclease XRN1 play critical roles in mRNA decay. Using immunohistochemistry with antibodies against DIS3L2 and XRN1, we examined the brains of patients with polyQ diseases and INIBD and normal control subjects. In controls, immunoreactivity for DIS3L2 and XRN1 was found in the neuronal cytoplasm and neuropil, respectively. In INIBD, immunoreactivity for DIS3L2 and XRN1 was present in neuronal and glial nuclear inclusions. Co-localization of ubiquitin and DIS3L2 or XRN1 was demonstrated in these inclusions. In polyQ diseases, however, nuclear inclusions were immunonegative for DIS3L2 and XRN1. These findings suggest that sequestration of exoribonucleases to nuclear inclusions may be related to the pathogenesis of INIBD.