Pre-spliceosomal binding of U1 small nuclear ribonucleoprotein (RNP) and heterogenous nuclear RNP E1 is associated with suppression of a growth hormone receptor pseudoexon
Pre-spliceosomal binding of U1 small nuclear ribonucleoprotein (RNP) and heterogenous nuclear RNP E1 is associated with suppression of a growth hormone receptor pseudoexon
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DOI：
10.1210/me.2007-0038
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发表时间：
2007-10-01
影响因子：
--
通讯作者：
Chew, Shern L.
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文献类型：
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作者：
Akker, Scott A.;Misra, Shivani;Chew, Shern L.
伪外显子经常出现在人类基因组中。本文描述了生长激素受体基因中的一个伪外显子。这种假外显子的不适当激活会导致Laron综合征。使用体外剪接实验，伪外显子沉默被证明需要弱的5‘伪剪接位点和伪外显子内剪接沉默元件的组合。免疫沉淀实验表明，剪接前小体复合体中异源核糖核蛋白E1(HnRNP E1)和U1小核糖核蛋白(SnRNP)的特异性结合与伪外显子剪接的沉默有关。在培养细胞中的RNA干扰实验进一步支持了hnRNP E1的可能作用。与其他三个伪外显子的免疫沉淀实验表明，U1 SnRNP的剪接体前结合是抑制伪外显子的一种潜在的一般机制。
Pseudoexons occur frequently in the human genome. This paper characterizes a pseudoexon in the GH receptor gene. Inappropriate activation of this pseudoexon causes Laron syndrome. Using in vitro splicing assays, pseudoexon silencing was shown to require a combination of a weak 5 ' pseudosplice- site and splicing silencing elements within the pseudoexon. Immunoprecipitation experiments showed that specific binding of heterogenous nuclear ribonucleoprotein E1 ( hnRNP E1) and U1 small nuclear ribonucleoprotein ( snRNP) in the pre- spliceosomal complex was associated with silencing of pseudoexon splicing. The possible role of hnRNP E1 was further supported by RNA interference experiments in cultured cells. Immunoprecipitation experiments with three other pseudoexons suggested that pre- spliceosomal binding of U1 snRNP is a potential general mechanism of suppression of pseudoexons.