Regulatory RNA binding proteins contribute to the transcriptome-wide splicing alterations in human cellular senescence.
Regulatory RNA binding proteins contribute to the transcriptome-wide splicing alterations in human cellular senescence.
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调节性RNA结合蛋白导致人类细胞衰老中转录组范围内的剪接改变
DOI：
10.18632/aging.101485
复制
发表时间：
2018-06-24
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Dong Q;Wei L;Zhang MQ;Wang X
在某些细胞衰老过程中观察到了mRNA剪接的失调。然而，各种类型的衰老所共有的整个转录组上的常见剪接变化却知之甚少。为了在全基因组水平上系统地识别衰老相关的转录变化，我们从公共数据库中收集了不同类型的人类细胞的RNA测序数据，并进行了荟萃分析。首先，我们发现一组RNA结合蛋白在不同的衰老样本中持续下调，并鉴定了406个与衰老相关的共同差异剪接事件。然后，通过对其RNA结合信息的丰富分析，包括基序扫描和增强的交联免疫沉淀数据，预测了8种差异表达的RNA结合蛋白调节这些与衰老相关的剪接改变。此外，我们构建了可能有助于衰老相关生物过程的剪接调控模块。最后，证实了通过shRNAs在HepG2细胞中敲除预测的衰老相关剪接调节因子可以导致衰老样剪接变化。综上所述，我们的工作展示了mRNA剪接开关的广泛常见变化，并检测到它们在衰老过程中的中央调节RNA结合蛋白。这些发现将有助于更好地理解细胞衰老中的协调剪接变化。
Dysregulation of mRNA splicing has been observed in certain cellular senescence process. However, the common splicing alterations on the whole transcriptome shared by various types of senescence are poorly understood. In order to systematically identify senescence-associated transcriptomic changes in genome-wide scale, we collected RNA sequencing datasets of different human cell types with a variety of senescence-inducing methods from public databases and performed meta-analysis. First, we discovered that a group of RNA binding proteins were consistently down-regulated in diverse senescent samples and identified 406 senescence-associated common differential splicing events. Then, eight differentially expressed RNA binding proteins were predicted to regulate these senescence-associated splicing alterations through an enrichment analysis of their RNA binding information, including motif scanning and enhanced cross-linking immunoprecipitation data. In addition, we constructed the splicing regulatory modules that might contribute to senescence-associated biological processes. Finally, it was confirmed that knockdown of the predicted senescence-associated potential splicing regulators through shRNAs in HepG2 cell line could result in senescence-like splicing changes. Taken together, our work demonstrated a broad range of common changes in mRNA splicing switches and detected their central regulatory RNA binding proteins during senescence. These findings would help to better understand the coordinating splicing alterations in cellular senescence.
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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：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
3
作者：
Hibbs MA;Dirksen NC;Li K;Troyanskaya OG
通讯作者：
Troyanskaya OG
影响因子：
5.3
作者：
Holly, Alice C.;Melzer, David;Harries, Lorna W.
通讯作者：
Harries, Lorna W.