An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer's disease brain samples.
An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer's disease brain samples.
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DOI：
10.1242/dmm.009761
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发表时间：
2013-03
影响因子：
4.3
通讯作者：
Pagano A
中科院分区：
文献类型：
--
作者：
Ciarlo E;Massone S;Penna I;Nizzari M;Gigoni A;Dieci G;Russo C;Florio T;Cancedda R;Pagano A
最近的研究表明，分拣蛋白相关受体1（SORL 1）是迟发性阿尔茨海默病（AD）的危险基因，尽管其在这种疾病的病因学和/或进展中的作用尚未完全了解。在这里，我们报告了一个非编码（NC）RNA（以下简称为51 A），映射在SORL 1基因的内含子1的反义配置的发现。51 A表达驱动SORL 1从典型长蛋白变体A的合成到可变剪接蛋白形式的剪接转变。这一过程导致SORL 1变体A的合成减少，与淀粉样前体蛋白（APP）加工受损相关，导致Aβ形成增加。有趣的是，我们发现51 A在人脑中表达，在阿尔茨海默病患者的大脑皮层中经常上调。总之，这些发现证明了一种新的ncRNA依赖性调控途径，可能对神经退行性疾病具有相关意义。
Recent studies indicated that sortilin-related receptor 1 (SORL1) is a risk gene for late-onset Alzheimer's disease (AD), although its role in the aetiology and/or progression of this disorder is not fully understood. Here, we report the finding of a non-coding (nc) RNA (hereafter referred to as 51A) that maps in antisense configuration to intron 1 of the SORL1 gene. 51A expression drives a splicing shift of SORL1 from the synthesis of the canonical long protein variant A to an alternatively spliced protein form. This process, resulting in a decreased synthesis of SORL1 variant A, is associated with impaired processing of amyloid precursor protein (APP), leading to increased Aβ formation. Interestingly, we found that 51A is expressed in human brains, being frequently upregulated in cerebral cortices from individuals with Alzheimer's disease. Altogether, these findings document a novel ncRNA-dependent regulatory pathway that might have relevant implications in neurodegeneration.
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新的小核RNA基因样转录单元作为调节转录的来源。
影响因子：
4.5
作者：
Pagano A;Castelnuovo M;Tortelli F;Ferrari R;Dieci G;Cancedda R
通讯作者：
Cancedda R
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Schaller, HC
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作者：
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通讯作者：
Petersen, CM
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作者：
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