图 书 馆
血清microRNA图谱显示脆性X相关蛋白在ALS中的作用Serum microRNA-profiles indicate a role of Fragile-X-related proteins for ALS |
|
| 课程网址: | http://videolectures.net/encals2017_freischmidt_microRNA_profiles... |
| 主讲教师: | Axel Freischmidt |
| 开课单位: | 乌尔姆大学 |
| 开课时间: | 2017-07-21 |
| 课程语种: | 英语 |
| 中文简介: |  |
| 课程简介: | In previous studies we identified a subset of downregulated serum microRNAs (miRNAs) in familial and a majority (60%) of sporadic ALS patients that was already evident in pre-clinical mutation carriers. A common 5-nucleotide-sequence motif (GDCGG; D = G, A or U) was highly significantly enriched in the downregulated miRNAs indicating the deregulation/malfunction of one or several specific RNA-binding protein(s). Using miRNA-pulldown assays in lysates of HEK293 cells followed by mass spectrometric identification and quantification of precipitated proteins, we identified 37 proteins specifically associated with the GDCGG-motif. Direct and specific binding to miRNAs with the GDCGG-motif of two of the top candidate proteins, FXR1 and FXR2, was confirmed by biochemical assays. Binding domains could be mapped to the RGG-domain of FXR1 and the second RG-domain of FXR2. The third member of the Fragile-X-related protein family, FMRP, causes Fragile-X mental retardation when absent and has already been implicated in ALS pathology. Although not a top candidate protein in our miRNA-pulldown assays, we show direct and specific binding of FMRP to miRNAs with the GDCGG-motif via its RGG-domain highly homologous to the RGG/RG-domains of FXR1 and FXR2, respectively. In vitro binding studies on a transcriptome-wide scale using miRNA-arrays identified the member of the FragileX-related protein family most likely responsible for altered miRNA-profiles in ALS and expression analysis and neuropathological studies will be employed to validate its role in ALS pathogenesis. |
| 关 键 词: | ALS患者; 神经病理学研究; miRNA |
| 课程来源: | 视频讲座网 |
| 数据采集: | 2021-12-25：zkj |
| 最后编审: | 2021-12-25：zkj |
| 阅读次数: | 35 |