The domain structure and distribution of Alu elements in long noncoding RNAs and mRNAs.
The domain structure and distribution of Alu elements in long noncoding RNAs and mRNAs.
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DOI：
10.1261/rna.048280.114
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Caffrey DR
中科院分区：
文献类型：
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作者：
Kim EZ;Wespiser AR;Caffrey DR
大约75%的人类基因组被转录，并且这些剪接的转录物中的许多含有灵长类特异性Alu元件，其是人类基因组中最丰富的移动的元件。大多数外显子Alu元件位于长链非编码RNA（lncRNA）和mRNA的非翻译区，其中一些执行分子功能。为了进一步评估Alu元件被重新利用为功能性RNA结构域的潜力，我们研究了Alu元件在拼接转录本中的分布和进化。我们的分析表明，Alu元素在mRNA和lncRNA中的代表性不足，这表明在人口中出现的大多数外显子Alu元素是罕见的或有害的RNA功能。当mRNA和lncRNA保留外显子化的Alu元件时，它们对Alu二聚体、左单体和右单体具有明显的偏好。当它们的基因在富含Alu的区域内复制时，mRNA通常获得Alu元件。在lncRNA中，反向Alu元件显著富集，并且不限于3′和5′末端。lncRNA和mRNA主要包含在灵长类进化中相对早期扩增的Alu J和S亚家族。Alu J亚家族通常在lncRNA中过度表达，而Alu S二聚体在mRNA中过度表达。Alu二聚体的序列倾向于在lncRNA和mRNA两者中受到限制，而左单体和右单体被限制在特定的Alu亚家族和RNA类别内。总的来说，这些发现表明，含Alu的RNA能够形成稳定的结构，其中一些Alu结构域可能具有新的生物学功能。
Approximately 75% of the human genome is transcribed and many of these spliced transcripts contain primate-specific Alu elements, the most abundant mobile element in the human genome. The majority of exonized Alu elements are located in long noncoding RNAs (lncRNAs) and the untranslated regions of mRNA, with some performing molecular functions. To further assess the potential for Alu elements to be repurposed as functional RNA domains, we investigated the distribution and evolution of Alu elements in spliced transcripts. Our analysis revealed that Alu elements are underrepresented in mRNAs and lncRNAs, suggesting that most exonized Alu elements arising in the population are rare or deleterious to RNA function. When mRNAs and lncRNAs retain exonized Alu elements, they have a clear preference for Alu dimers, left monomers, and right monomers. mRNAs often acquire Alu elements when their genes are duplicated within Alu-rich regions. In lncRNAs, reverse-oriented Alu elements are significantly enriched and are not restricted to the 3′ and 5′ ends. Both lncRNAs and mRNAs primarily contain the Alu J and S subfamilies that were amplified relatively early in primate evolution. Alu J subfamilies are typically overrepresented in lncRNAs, whereas the Alu S dimer is overrepresented in mRNAs. The sequences of Alu dimers tend to be constrained in both lncRNAs and mRNAs, whereas the left and right monomers are constrained within particular Alu subfamilies and classes of RNA. Collectively, these findings suggest that Alu-containing RNAs are capable of forming stable structures and that some of these Alu domains might have novel biological functions.