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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A Postnatal Switch Of Celf And Mbnl Proteins Reprograms Alternative Splicing In The Developing Heart
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A Postnatal Switch Of Celf And Mbnl Proteins Reprograms Alternative Splicing In The Developing Heart

机译：小牛和Mbnl蛋白的产后开关重新编程发育中的心脏的替代剪接。

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摘要

From a large-scale screen using splicing microarrays and RT-PCR, we identified 63 alternative splicing (AS) events that are coordinated in 3 distinct temporal patterns during mouse heart development. More than half of these splicing transitions are evolutionarily conserved between mouse and chicken. Computational analysis of the introns flanking these splicing events identified enriched and conserved motifs including binding sites for CUGBP and ETR-3-like factors (CELF), muscleblind-like (MBNL) and Fox proteins. We show that CELF proteins are down-regulated > 10-fold during heart development, and MBNL1 protein is concomitantly up-regulated nearly 4-fold. Using transgenic and knockout mice, we show that reproducing the embryonic expression patterns for CUGBP1 and MBNL1 in adult heart induces the embryonic splicing patterns for more than half of the developmentally regulated AS transitions. These findings indicate that CELF and MBNL proteins are determinative for a large subset of splicing transitions that occur during postnatal heart development.
机译：从使用拼接微阵列和RT-PCR的大规模屏幕中，我们确定了63个替代拼接（AS）事件，这些事件在小鼠心脏发育过程中以3种不同的时间模式进行了协调。这些剪接过渡的一半以上在小鼠和鸡之间在进化上是保守的。对这些剪接事件侧翼的内含子的计算分析确定了丰富和保守的基序，包括CUGBP和ETR-3样因子（CELF），肌盲样（MBNL）和Fox蛋白的结合位点。我们表明，CELF蛋白在心脏发育过程中被下调> 10倍，而MBNL1蛋白则同时被上调了近4倍。使用转基因和基因敲除小鼠，我们表明，在成年心脏中复制CUGBP1和MBNL1的胚胎表达模式可诱导一半以上的发育调控的AS过渡的胚胎剪接模式。这些发现表明，CELF和MBNL蛋白可决定出生后心脏发育过程中发生的大部分剪接过渡。

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