Novel functional role of CA repeats and hnRNP L in RNA stability
Novel functional role of CA repeats and hnRNP L in RNA stability
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DOI：
10.1261/rna.5660803
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发表时间：
2003-08-01
期刊：
影响因子：
4.5
通讯作者：
Bindereif, A
中科院分区：
文献类型：
--
作者：
Hui, JY;Reither, G;Bindereif, A
CA二核苷酸重复序列在人类基因组中非常常见。我们最近已经证明，多态性CA重复内含子13的人内皮型一氧化氮合酶（eNOS）基因的功能作为一个不寻常的，长度依赖性剪接增强子。CA重复序列增强子的活性需要hnRNP L的特异性结合。在这里，我们表明，在没有结合的hnRNP L的情况下，前mRNA直接在CA重复序列的上游被切割。重组hnRNP L的添加恢复RNA稳定性。CA重复序列对于5'相邻RNA序列中的这种特异性切割是必要的和足够的。我们的结论是，除了它的作用作为一个剪接激活剂-hnRNP L可以在体外作为一个序列特异性RNA保护因子。基于CA重复序列在人类基因组中的广泛丰度，这可能代表了这种丰富的hnRNP蛋白质的一种新的、普遍重要的作用。
CA dinucleotide repeat sequences are very common in the human genome. We have recently demonstrated that the polymorphic CA repeats in intron 13 of the human endothelial nitric oxide synthase (eNOS) gene function as an unusual, length-dependent splicing enhancer. The CA repeat enhancer requires for its activity specific binding of hnRNP L. Here we show that in the absence of bound hnRNP L, the pre-mRNA is cleaved directly upstream of the CA repeats. The addition of recombinant hnRNP L restores RNA stability. CA repeats are both necessary and sufficient for this specific cleavage in the 5' adjacent RNA sequence. We conclude that-in addition to its role as a splicing activator-hnRNP L can act in vitro as a sequence-specific RNA protection factor. Based on the wide abundance of CA repetitive sequences in the human genome, this may represent a novel, generally important role of this abundant hnRNP protein.