Widespread cleavage of A-to-I hyperediting substrates
Widespread cleavage of A-to-I hyperediting substrates
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DOI：
10.1261/rna.1581809
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发表时间：
2009-09-01
期刊：
影响因子：
4.5
通讯作者：
Eisenberg, Eli
中科院分区：
文献类型：
--
作者：
Osenberg, Sivan;Dominissini, Dan;Eisenberg, Eli
A-to-I RNA编辑是在双链细胞和病毒RNA中将腺苷转化为肌苷。最近，大量的人类转录本，影响成千上万的基因，已被报道。这些编辑位点中的大多数局限于分子内发夹双链RNA（dsRNA）结构，其通过相邻的、定向的、灵长类动物特异性Alu重复配对形成。这种广泛的修改的生物学含义仍然是一个谜。许多研究表明，经过大量编辑的转录本通常保留在细胞核中。最近的一项研究发现，小鼠Slc 7a 2基因转录本中的编辑区域在应激时被转录后切割，使mRNA释放到细胞质中，然后进行翻译。在这里，我们的目标是测试这种情况是否可能是相关的许多其他hyperedited铝目标。公开可用的mRNA和表达的序列标签数据的生物信息学分析提供的证据表明，相邻的，以丙氨酸为导向的，Alu元件通常在含有反向重复序列的区域的两端被切割，然后在反向重复序列的两侧重新连接转录本的两个部分，导致几乎不含肌苷的mRNA产物。剪接片段在相同基因的转录物之间变化，并且不被典型剪接信号序列侧接。这些事件的组织分布似乎与已知的A-to-I编辑模式相关，表明它取决于正在编辑的dsRNA结构。结果通过聚合酶链反应和克隆数据进行了实验验证。提供了566个人类和107个小鼠推定切割位点的数据库。
A-to-I RNA editing is the conversion of adenosine to inosine in double-stranded cellular and viral RNAs. Recently, abundant hyperediting of human transcripts, affecting thousands of genes, has been reported. Most of these editing sites are confined to intramolecular hairpin double-stranded RNA (dsRNA) structures formed by pairing of neighboring, reversely oriented, primate-specific Alu repeats. The biological implication of this extensive modification is still a mystery. A number of studies have shown that heavily edited transcripts are often retained in the nucleus. A recent study found that the edited region in transcripts of the mouse Slc7a2 gene is post-transcriptionally cleaved upon stress, enabling the release of the mRNA to the cytoplasm, followed by its translation. Here, we aim to test whether this scenario might be relevant for many other hyperedited Alu targets. Bioinformatics analysis of publicly available mRNA and expressed sequence tag data provides evidence showing that neighboring, reversely oriented, Alu elements are often cleaved at both ends of the region harboring the inverted repeats followed by rejoining of the two parts of the transcript on both sides of the inverted repeats, resulting in almost inosine-free mRNA products. Deleted segments vary among transcripts of the same gene and are not flanked by the canonical splicing signal sequences. The tissue distribution of these events seems to correlate with known A-to-I editing patterns, suggesting that it depends on the dsRNA structure being edited. Results are experimentally verified by polymerase chain reaction and cloning data. A database of 566 human and 107 mouse putative cleavage loci is supplied.