Nuclear factor TDP-43 can affect selected microRNA levels
Nuclear factor TDP-43 can affect selected microRNA levels
复制标题
DOI：
10.1111/j.1742-4658.2010.07643.x
复制
发表时间：
2010-05-01
期刊：
影响因子：
5.4
通讯作者：
Baralle, Francisco
中科院分区：
文献类型：
--
作者：
Buratti, Emanuele;De Conti, Laura;Baralle, Francisco
最近，TDP-43 被描述为在患有多种神经退行性疾病（例如额颞叶变性和肌萎缩侧索硬化症）的患者大脑中发现的包涵体的主要成分。 TDP-43 是一种普遍存在的蛋白质，其特定功能可能对于确定其致病作用至关重要。除了参与转录、剪接和 mRNA 稳定性之外，TDP-43 还被描述为 Drosha 相关蛋白。然而，我们对 TDP-43 在 microRNA (miRNA) 合成途径中作用的了解仅限于上述关联。在这里，我们首次报告了培养细胞中 TDP-43 敲低后总 miRNA 群体发生的变化。特别是，我们观察到 let-7b 和 miR-663 表达水平分别下调和上调。有趣的是，两种 miRNA 都能够在不同位置直接结合 TDP-43：在 miRNA 序列本身 (let-7b) 内或在发夹前体 (miR-663) 内。使用微阵列数据和实时 PCR，我们还鉴定了几种候选转录本，其表达水平选择性地受到这些 TDP-43-miRNA 相互作用的影响。
TDP-43 has recently been described as the major component of the inclusions found in the brain of patients with a variety of neurodegenerative diseases, such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. TDP-43 is a ubiquitous protein whose specific functions are probably crucial to establishing its pathogenic role. Apart from its involvement in transcription, splicing and mRNA stability, TDP-43 has also been described as a Drosha-associated protein. However, our knowledge of the role of TDP-43 in the microRNA (miRNA) synthesis pathway is limited to the association mentioned above. Here we report for the first time which changes occur in the total miRNA population following TDP-43 knockdown in culture cells. In particular, we have observed that let-7b and miR-663 expression levels are down- and upregulated, respectively. Interestingly, both miRNAs are capable of binding directly to TDP-43 in different positions: within the miRNA sequence itself (let-7b) or in the hairpin precursor (miR-663). Using microarray data and real-time PCR we have also identified several candidate transcripts whose expression levels are selectively affected by these TDP-43-miRNA interactions.