Expression analysis of the long non-coding RNA antisense to Uchl1 (AS Uchl1) during dopaminergic cells' differentiation in vitro and in neurochemical models of Parkinson's disease.
Expression analysis of the long non-coding RNA antisense to Uchl1 (AS Uchl1) during dopaminergic cells' differentiation in vitro and in neurochemical models of Parkinson's disease.
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DOI：
10.3389/fncel.2015.00114
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发表时间：
2015
影响因子：
5.3
通讯作者：
Gustincich S
中科院分区：
文献类型：
--
作者：
Carrieri C;Forrest AR;Santoro C;Persichetti F;Carninci P;Zucchelli S;Gustincich S
反义(AS)转录本是从相反的链转录到正义(S)基因形成S/AS对的rna分子。最显著的构型是当lncRNA与蛋白质编码基因反义时。越来越多的证据证明，反义转录可以在不同的调控水平上调控正义基因的表达。然而，它对大脑功能和神经退行性疾病的贡献仍不清楚。我们最近发现UCHL1是小鼠泛素羧基末端水解酶L1(UCHL1)基因的反义基因(UCHL1)，该基因是UCHL1/PARK5的合成基因。这在罕见的早发性家族性帕金森病(PD)病例中会发生突变，许多神经退行性疾病中都有UCHL1活性丧失的报道。重要的是，对UCHL1表达的操纵已被认为是治疗干预的工具。AS UCHL1通过增加翻译诱导UCHL1的表达。它是SINEUPs(SINEB2 Sequence to Up-Reguling Transaction)的代表成员，SINEUPs是一类新的天然反义lncRNAs，激活其正义基因的翻译。在这里，我们利用FANTOM5数据集来识别与UchL1上的S/AS对相关的转录起始点。我们发现，由于UCHL1的表达受Nurr1的调控，Nurr1是参与多巴胺能细胞分化和维持的主要转录因子。此外，在体外和体内的帕金森病神经化学模型中，由于Uch1 RNA水平强烈下调。这项工作将UCHL1 RNA定位为Nurr1依赖的基因网络的组成部分和细胞应激的目标，扩展了我们对反义转录在大脑中的作用的理解。
Antisense (AS) transcripts are RNA molecules that are transcribed from the opposite strand to sense (S) genes forming S/AS pairs. The most prominent configuration is when a lncRNA is antisense to a protein coding gene. Increasing evidences prove that antisense transcription may control sense gene expression acting at distinct regulatory levels. However, its contribution to brain function and neurodegenerative diseases remains unclear. We have recently identified AS Uchl1 as an antisense to the mouse Ubiquitin carboxy-terminal hydrolase L1 (Uchl1) gene (AS Uchl1), the synthenic locus of UCHL1/PARK5. This is mutated in rare cases of early-onset familial Parkinson's Disease (PD) and loss of UCHL1 activity has been reported in many neurodegenerative diseases. Importantly, manipulation of UchL1 expression has been proposed as tool for therapeutic intervention. AS Uchl1 induces UchL1 expression by increasing its translation. It is the representative member of SINEUPs (SINEB2 sequence to UP-regulate translation), a new functional class of natural antisense lncRNAs that activate translation of their sense genes. Here we take advantage of FANTOM5 dataset to identify the transcription start sites associated to S/AS pair at Uchl1 locus. We show that AS Uchl1 expression is under the regulation of Nurr1, a major transcription factor involved in dopaminergic cells' differentiation and maintenance. Furthermore, AS Uch1 RNA levels are strongly down-regulated in neurochemical models of PD in vitro and in vivo. This work positions AS Uchl1 RNA as a component of Nurr1-dependent gene network and target of cellular stress extending our understanding on the role of antisense transcription in the brain.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
64.8
作者：
Carrieri, Claudia;Cimatti, Laura;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
14.8
作者：
Jackson-Lewis, Vernice;Przedborski, Serge
通讯作者：
Przedborski, Serge
DOI：
10.1073/pnas.0813216106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Biagioli, Marta;Pinto, Milena;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
4.8
作者：
Choi, J;Levey, AI;Li, L
通讯作者：
Li, L