A survey of RNA editing in human brain
A survey of RNA editing in human brain
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DOI：
10.1101/gr.2951204
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发表时间：
2004-12-01
期刊：
影响因子：
7
通讯作者：
Stratton, MR
中科院分区：
文献类型：
--
作者：
Blow, M;Futreal, PA;Stratton, MR
我们通过将人脑cDNA文库中的克隆序列与参考的人类基因组序列以及来自同一个体的基因组DNA进行比较，对人脑中的RNA编辑进行了调查。在构建文库的RNA样本中，从调查的>；3Mb中编辑出-1：2000核苷酸。所有的编辑都是腺苷到肌苷(A->；I)，并且主要在内含子和基因间RNA中。在已翻译的外显子中没有发现编辑，而在未翻译的外显子中几乎没有编辑。大多数编辑都是高拷贝重复，通常是ALU。对编辑序列附近的基因组的分析有力地支持了这一观点，即大多数A->；I编辑是形成具有反向拷贝的分子内双链RNA的基础。通过同一内含子内序列的两个反向拷贝的存在、两个序列彼此接近(优选在2kb以内)以及附近高密度的反向拷贝，增加了编辑的可能性。编辑显示出序列偏好，并且不太可能在腺苷3‘到鸟苷，而更有可能在腺苷5到鸟苷。通过BLAST比对作为已知编辑基础的双链RNA分子的模拟表明，在A：C错配时编辑A--&>I的可能性比在其他错配或A：U匹配时编辑的可能性更大。然而，由于双链RNA中的A：U匹配比所有错配更常见，因此总体而言，编辑的可能效果是增加双链RNA中的错配数量。
We have conducted a survey of RNA editing in human brain by comparing sequences of clones from a human brain cDNA library to the reference human genome sequence and to genomic DNA from the same individual. In the RNA sample from which the library was constructed, -1:2000 nucleotides were edited out of >3 Mb surveyed. All edits were adenosine to inosine (A-->I) and were predominantly in intronic and in intergenic RNAs. No edits were found in translated exons and few in untranslated exons. Most edits were in high-copy-number repeats, usually Alus. Analysis of the genome in the vicinity of edited sequences strongly supports the idea that formation of intramolecular double-stranded RNA with an inverted copy underlies most A-->I editing. The likelihood of editing is increased by the presence of two inverted copies of a sequence within the same intron, proximity of the two sequences to each other (preferably within 2 kb), and by a high density of inverted copies in the vicinity. Editing exhibits sequence preferences and is less likely at an adenosine 3' to a guanosine and more likely at an adenosine 5 to a guanosine. Simulation by BLAST alignment of the double-stranded RNA molecules that underlie known edits indicates that there is a greater likelihood of A-->I editing at A:C mismatches than editing at other mismatches or at A:U matches. However, because A:U matches in double-stranded RNA are more common than all mismatches, overall the likely effect of editing is to increase the number of mismatches in double-stranded RNA.