Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer's disease.
Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer's disease.
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DOI：
10.1038/s41467-017-00867-z
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发表时间：
2017-10-13
影响因子：
16.6
通讯作者：
Najafabadi HS
中科院分区：
文献类型：
--
作者：
Alkallas R;Fish L;Goodarzi H;Najafabadi HS
mRNA的丰度主要由RNA转录和衰变的速率决定。在这里，我们提出了一种无偏估计的差异mRNA衰减率从RNA测序数据建模的mRNA代谢动力学的方法。我们表明，在所有主要的人体组织测试，特别是在中枢神经系统，许多途径的mRNA稳定性水平的调节。我们提出了一个由两个RNA结合蛋白和四个microRNA组成的简约调控模型，该模型调节大脑的mRNA稳定性，这表明RBFOX蛋白与阿尔茨海默病之间存在新的联系。我们发现RBFOX 1的下调导致编码突触传递蛋白的mRNA的不稳定，这可能导致阿尔茨海默病中突触功能的丧失。RBFOX 1下调更可能发生在老年人和女性个体中，这与阿尔茨海默病与年龄和性别的相关性一致。“mRNA丰度由转录和衰变速率决定。在这里，作者提出了一种方法，用于从RNA-seq数据和大脑中的模型mRNA稳定性估计差异mRNA衰减率，这表明mRNA稳定性与阿尔茨海默病之间存在联系。
The abundance of mRNA is mainly determined by the rates of RNA transcription and decay. Here, we present a method for unbiased estimation of differential mRNA decay rate from RNA-sequencing data by modeling the kinetics of mRNA metabolism. We show that in all primary human tissues tested, and particularly in the central nervous system, many pathways are regulated at the mRNA stability level. We present a parsimonious regulatory model consisting of two RNA-binding proteins and four microRNAs that modulate the mRNA stability landscape of the brain, which suggests a new link between RBFOX proteins and Alzheimer’s disease. We show that downregulation of RBFOX1 leads to destabilization of mRNAs encoding for synaptic transmission proteins, which may contribute to the loss of synaptic function in Alzheimer’s disease. RBFOX1 downregulation is more likely to occur in older and female individuals, consistent with the association of Alzheimer’s disease with age and gender. “mRNA abundance is determined by the rates of transcription and decay. Here, the authors propose a method for estimating the rate of differential mRNA decay from RNA-seq data and model mRNA stability in the brain, suggesting a link between mRNA stability and Alzheimer’s disease.”
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
46.9
作者：
Gaidatzis, Dimos;Burger, Lukas;Stadler, Michael B.
通讯作者：
Stadler, Michael B.
影响因子：
16.8
作者：
Ameur, Adam;Zaghlool, Ammar;Feuk, Lars
通讯作者：
Feuk, Lars
影响因子：
23.9
作者：
Delaloy C;Liu L;Lee JA;Su H;Shen F;Yang GY;Young WL;Ivey KN;Gao FB
通讯作者：
Gao FB