SAFB1 is a DNA and RNA binding protein that is highly expressed in the cerebellum and hippocampus and is involved in the processing of coding and non‐coding RNAs, splicing and dendritic function. We analyzed SAFB1 expression in the post‐mortem brain tissue of spinocerebellar ataxia (SCA), Huntington’s disease (HD), Multiple sclerosis (MS), Parkinson’s disease patients and controls. In SCA cases, the expression of SAFB1 in the nucleus was increased and there was abnormal and extensive expression in the cytoplasm where it co‐localized with the markers of Purkinje cell injury. Significantly, no SAFB1 expression was found in the cerebellar neurons of the dentate nucleus in control or MS patients; however, in SCA patients, SAFB1 expression was increased significantly in both the nucleus and cytoplasm of dentate neurons. In HD, we found that SAFB1 expression was increased in the nucleus and cytoplasm of striatal neurons; however, there was no SAFB1 staining in the striatal neurons of controls. In PD substantia nigra, we did not see any changes in neuronal SAFB1 expression. iCLIP analysis found that SAFB1 crosslink sites within ATXN1 RNA were adjacent to the start and within the glutamine repeat sequence. Further investigation found increased binding of SAFB1 to pathogenic ATXN1‐85Q mRNA. These novel data strongly suggest SAFB1 contributes to the etiology of SCA and Huntington’s chorea and that it may be a pathological marker of polyglutamine repeat expansion diseases.

中文翻译：

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脊髓小脑性共济失调和亨廷顿舞蹈病中支架附着因子 1 的异常表达和定位。

SAFB1 是一种 DNA 和 RNA 结合蛋白，在小脑和海马中高表达，参与编码和非编码 RNA 的加工、剪接和树突功能。我们分析了脊髓小脑性共济失调 (SCA)、亨廷顿病 (HD)、多发性硬化症 (MS)、帕金森病患者和对照的死后脑组织中的 SAFB1 表达。在 SCA 病例中，细胞核中 SAFB1 的表达增加，并且在与浦肯野细胞损伤标志物共定位的细胞质中存在异常和广泛的表达。值得注意的是，在对照或 MS 患者的齿状核小脑神经元中未发现 SAFB1 表达；然而，在 SCA 患者中，SAFB1 在齿状神经元的细胞核和细胞质中的表达均显着增加。在高清中，我们发现纹状体神经元细胞核和细胞质中SAFB1表达增加；然而，对照的纹状体神经元中没有 SAFB1 染色。在 PD 黑质中，我们没有看到神经元 SAFB1 表达的任何变化。iCLIP 分析发现 ATXN1 RNA 内的 SAFB1 交联位点与起始点相邻并位于谷氨酰胺重复序列内。进一步研究发现 SAFB1 与致病性 ATXN1-85Q mRNA 的结合增加。这些新数据强烈表明 SAFB1 有助于 SCA 和亨廷顿舞蹈病的病因学，并且它可能是多聚谷氨酰胺重复扩增疾病的病理标志物。我们没有看到神经元 SAFB1 表达的任何变化。iCLIP 分析发现 ATXN1 RNA 内的 SAFB1 交联位点与起始点相邻并位于谷氨酰胺重复序列内。进一步研究发现 SAFB1 与致病性 ATXN1-85Q mRNA 的结合增加。这些新数据强烈表明 SAFB1 有助于 SCA 和亨廷顿舞蹈病的病因学，并且它可能是多聚谷氨酰胺重复扩增疾病的病理标志物。我们没有看到神经元 SAFB1 表达的任何变化。iCLIP 分析发现 ATXN1 RNA 内的 SAFB1 交联位点与起始点相邻并位于谷氨酰胺重复序列内。进一步研究发现 SAFB1 与致病性 ATXN1-85Q mRNA 的结合增加。这些新数据强烈表明 SAFB1 有助于 SCA 和亨廷顿舞蹈病的病因学，并且它可能是多聚谷氨酰胺重复扩增疾病的病理标志物。