Barak Michal, Levanon Erez Y, Eisenberg Eli, Paz Nurit, Rechavi Gideon, Church George M, Mehr Ramit
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
Nucleic Acids Res. 2009 Nov;37(20):6905-15. doi: 10.1093/nar/gkp729. Epub 2009 Sep 8.
Adenosine-to-inosine (A-to-I) RNA editing alters the original genomic content of the human transcriptome and is essential for maintenance of normal life in mammals. A-to-I editing in Alu repeats is abundant in the human genome, with many thousands of expressed Alu sequences undergoing editing. Little is known so far about the contribution of Alu editing to transcriptome complexity. Transcripts derived from a single edited Alu sequence can be edited in multiple sites, and thus could theoretically generate a large number of different transcripts. Here we explored whether the combinatorial potential nature of edited Alu sequences is actually fulfilled in the human transcriptome. We analyzed datasets of editing sites and performed an analysis of a detailed transcript set of one edited Alu sequence. We found that editing appears at many more sites than detected by earlier genomic screens. To a large extent, editing of different sites within the same transcript is only weakly correlated. Thus, rather than finding a few versions of each transcript, a large number of edited variants arise, resulting in immense transcript diversity that eclipses alternative splicing as mechanism of transcriptome diversity, although with less impact on the proteome.
腺苷到次黄苷（A-to-I）的RNA编辑改变了人类转录组的原始基因组内容，对哺乳动物维持正常生命至关重要。人类基因组中Alu重复序列的A-to-I编辑很丰富，数千个表达的Alu序列会发生编辑。到目前为止，关于Alu编辑对转录组复杂性的贡献知之甚少。源自单个编辑后的Alu序列的转录本可在多个位点进行编辑，因此理论上可以产生大量不同的转录本。在这里，我们探讨了编辑后的Alu序列的组合潜在性质在人类转录组中是否真的存在。我们分析了编辑位点数据集，并对一个编辑后的Alu序列的详细转录本集进行了分析。我们发现，编辑出现的位点比早期基因组筛选检测到的要多得多。在很大程度上，同一转录本内不同位点的编辑之间仅有微弱的相关性。因此，出现的不是每个转录本的几个版本，而是大量编辑变体，从而导致巨大的转录本多样性，尽管对蛋白质组的影响较小，但这种多样性使可变剪接作为转录组多样性机制黯然失色。
