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首页> 外文期刊>Journal of Molecular and Cellular Cardiology >Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy
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Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy

机译:mRNA测序可确定心脏肥大中胎儿剪接变体的重新表达

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Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing of mRNA transcripts has been shown to be temporally regulated during heart development, leading us to consider whether fetal patterns of splicing also reappear during hypertrophy. We hypothesized that patterns of alternative splicing occurring during heart development are recapitulated during cardiac hypertrophy. Here we present a study of isoform expression during pressure-overload cardiac hypertrophy induced by 10. days of transverse aortic constriction (TAC) in rats and in developing fetal rat hearts compared to sham-operated adult rat hearts, using high-throughput sequencing of poly(A) tail mRNA. We find a striking degree of overlap between the isoforms expressed differentially in fetal and pressure-overloaded hearts compared to control: forty-four percent of the isoforms with significantly altered expression in TAC hearts are also expressed at significantly different levels in fetal hearts compared to control (P<. 0.001). The isoforms that are shared between hypertrophy and fetal heart development are significantly enriched for genes involved in cytoskeletal organization, RNA processing, developmental processes, and metabolic enzymes. Our data strongly support the concept that mRNA splicing patterns normally associated with heart development recur as part of the hypertrophic response to pressure overload. These findings suggest that cardiac hypertrophy shares post-transcriptional as well as transcriptional regulatory mechanisms with fetal heart development.
机译:心脏肥大在转录水平上已被很好地表征。在心脏肥大过程中,通常在胎儿心脏发育过程中通常表达的基因会重新表达,并且该胎儿基因程序被认为是肥大过程的关键组成部分。最近,已显示在心脏发育过程中,mRNA转录物的选择性剪接受到时间调节,这使我们考虑是否在肥大期间也会出现胎儿剪接模式。我们假设在心脏肥大过程中概括了在心脏发育过程中发生的选择性剪接模式。在这里,我们对高负荷测序的假手术成年大鼠心脏与假手术成年大鼠心脏相比,在大鼠和发育中的胎鼠心脏中,由大鼠10天的横向主动脉缩窄(TAC)诱导的压力超负荷心脏肥大期间的同工型表达研究。 (A)尾巴mRNA。我们发现,与对照组相比,胎儿和压力超负荷心脏中差异表达的同工型之间的重叠程度惊人:与对照组相比,TAC心脏中表达显着改变的同工型的百分之四十四也以明显不同的水平表达(P <.0.001)。肥大和胎儿心脏发育之间共享的同工型显着丰富了涉及细胞骨架组织,RNA加工,发育过程和代谢酶的基因。我们的数据强烈支持这样的概念,即通常与心脏发育相关的mRNA剪接模式作为对压力超负荷的肥大反应的一部分而再次出现。这些发现表明,心脏肥大与胎儿心脏发育共享转录后以及转录调控机制。

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