蛋白 N-精氨酸甲基转移酶的突变不是 FTLD-FUS 的病因。
Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS.
机构信息
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
出版信息
Neurobiol Aging. 2013 Sep;34(9):2235.e11-3. doi: 10.1016/j.neurobiolaging.2013.04.004. Epub 2013 Apr 28.
Abstract
The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine-glycine-glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.
摘要
肉瘤中融合的核蛋白（FUS）存在于神经退行性疾病额颞叶变性（FTLD-FUS）患者的一部分细胞质包涵体中。FUS 含有一个甲基化的精氨酸-甘氨酸-甘氨酸结构域，该结构域对于核内运输是必需的。最近的研究结果表明，FTLD-FUS 患者的这个结构域低甲基化。为了确定低甲基化的原因是否是蛋白质 N-精氨酸甲基转移酶（PRMTs）的突变所致，我们选择了 3 个候选基因（PRMT1、PRMT3 和 PRMT8），并对 20 例 FTLD-FUS 病例进行了完整的测序分析和实时聚合酶链反应 mRNA 表达分析。在我们的患者样本中未观察到突变或表达的统计学显著变化，表明 PRMTs 的缺陷不是 FTLD-FUS 的原因。
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本文引用的文献
1
Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS.精氨酸甲基化紧邻 PY-NLS 可调节 FUS 的 Transportin 结合和核输入。
EMBO J. 2012 Nov 14;31(22):4258-75. doi: 10.1038/emboj.2012.261. Epub 2012 Sep 11.
2
Transportin 1 accumulates specifically with FET proteins but no other transportin cargos in FTLD-FUS and is absent in FUS inclusions in ALS with FUS mutations.转运蛋白 1 特异性地与 FET 蛋白积聚，但在 FTLD-FUS 中没有其他转运蛋白货物，并且在 FUS 突变的 ALS 中 FUS 包涵体中不存在。
Acta Neuropathol. 2012 Nov;124(5):705-16. doi: 10.1007/s00401-012-1020-6. Epub 2012 Jul 28.
3
FET proteins in frontotemporal dementia and amyotrophic lateral sclerosis.额颞叶痴呆和肌萎缩侧索硬化症中的 FET 蛋白。
Brain Res. 2012 Jun 26;1462:40-3. doi: 10.1016/j.brainres.2011.12.010. Epub 2011 Dec 13.
4
Arginine methylation by PRMT1 regulates nuclear-cytoplasmic localization and toxicity of FUS/TLS harbouring ALS-linked mutations.PRMT1 介导的精氨酸甲基化调控携带 ALS 相关突变的 FUS/TLS 的核质定位和毒性。
Hum Mol Genet. 2012 Jan 1;21(1):136-49. doi: 10.1093/hmg/ddr448. Epub 2011 Sep 28.
5
FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutations.FET 蛋白 TAF15 和 EWS 是选择性标志物，可将 FUS 病理的 FTLD 与 FUS 突变的肌萎缩侧索硬化症区分开来。
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6
The most common type of FTLD-FUS (aFTLD-U) is associated with a distinct clinical form of frontotemporal dementia but is not related to mutations in the FUS gene.最常见的 FTLD-FUS 类型（aFTLD-U）与特定的额颞叶痴呆临床形式相关，但与 FUS 基因突变无关。
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10
Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.16号染色体上FUS/TLS基因的突变会导致家族性肌萎缩侧索硬化症。
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