Abnormal scaffold attachment factor 1 expression and localization in spinocerebellar ataxias and Huntington's chorea.
Abnormal scaffold attachment factor 1 expression and localization in spinocerebellar ataxias and Huntington's chorea.
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DOI：
10.1111/bpa.12872
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Uney JB
中科院分区：
文献类型：
--
作者：
Buckner N;Kemp KC;Scott HL;Shi G;Rivers C;Gialeli A;Wong LF;Cordero-LLana O;Allen N;Wilkins A;Uney JB
SAFB 1是一种DNA和RNA结合蛋白，在小脑和海马中高度表达，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组死后脑组织中SAFB 1的表达。在SCA病例中，SAFB 1在细胞核中的表达增加，并且在细胞质中存在异常和广泛的表达，其与浦肯野细胞损伤的标志物共定位。值得注意的是，在对照组或MS患者的齿状核小脑神经元中没有发现SAFB 1表达;然而，在SCA患者中，SAFB 1在齿状核神经元的细胞核和细胞质中的表达显著增加。在HD中，我们发现SAFB 1在纹状体神经元的细胞核和细胞质中表达增加;然而，在对照组的纹状体神经元中没有SAFB 1染色。在PD黑质，我们没有看到神经元SAFB 1表达的任何变化。iCLIP分析发现，ATXN 1 RNA内SAFB 1交联位点邻近起始位点并在谷氨酰胺重复序列内。进一步的研究发现SAFB 1与致病性ATXN 1 - 85 Q mRNA的结合增加。这些新的数据有力地表明，SAFB 1有助于SCA和亨廷顿舞蹈病的病因，它可能是多聚谷氨酰胺重复扩增疾病的病理标志物。
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.
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影响因子：
3.5
作者：
Lee YB;Baskaran P;Gomez-Deza J;Chen HJ;Nishimura AL;Smith BN;Troakes C;Adachi Y;Stepto A;Petrucelli L;Gallo JM;Hirth F;Rogelj B;Guthrie S;Shaw CE
通讯作者：
Shaw CE
影响因子：
14.9
作者：
Liu HW;Banerjee T;Guan X;Freitas MA;Parvin JD
通讯作者：
Parvin JD
影响因子：
34.7
作者：
Lee, Edward B.;Lee, Virginia M-Y;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
25
作者：
Johnson, Janel O.;Pioro, Erik P.;Boehringer, Ashley;Chia, Ruth;Feit, Howard;Renton, Alan E.;Pliner, Hannah A.;Abramzon, Yevgeniya;Marangi, Giuseppe;Winborn, Brett J.;Gibbs, J. Raphael;Nalls, Michael A.;Morgan, Sarah;Shoai, Maryam;Hardy, John;Pittman, Alan;Orrell, Richard W.;Malaspina, Andrea;Sidle, Katie C.;Fratta, Pietro;Harms, Matthew B.;Baloh, Robert H.;Pestronk, Alan;Weihl, Conrad C.;Rogaeva, Ekaterina;Zinman, Lorne;Drory, Vivian E.;Borghero, Giuseppe;Mora, Gabriele;Calvo, Andrea;Rothstein, Jeffrey D.;Drepper, Carsten;Sendtner, Michael;Singleton, Andrew B.;Taylor, J. Paul;Cookson, Mark R.;Restagno, Gabriella;Sabatelli, Mario;Bowser, Robert;Chio, Adriano;Traynor, Bryan J.
通讯作者：
Traynor, Bryan J.
影响因子：
6.4
作者：
Marti, Eulalia
通讯作者：
Marti, Eulalia