Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome.

Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome.
复制标题

DOI:
10.1371/journal.pbio.0020391
复制
发表时间:
2004-12
期刊:
影响因子:
9.8
通讯作者:
Maas S
Maas S
中科院分区:
生物学1区
文献类型:
--
作者:
Athanasiadis A;Rich A;Maas S

文献摘要

参考文献

被引文献

相似文献

通过腺苷脱氨基作用的RNA编辑通过RNA序列中单个核苷酸的转录后修饰产生RNA和蛋白质多样性。尽管有证据表明应该存在更多的哺乳动物A-to-I编辑基因,但很少有哺乳动物A-to-I编辑基因被发现。在这里,我们确定了分子内的Alu元件对作为在人类转录组中编辑的主要目标。通过对超过100,000种人类mRNA进行更广泛的计算分析,扩展了43个基因的实验演示。我们发现,1,445种人类mRNA(1.4%)在超过14,500个位点进行RNA编辑,我们的数据进一步表明,绝大多数前体mRNA(超过85%)被编辑机制靶向于内含子。含反义RNA的mRNA的编辑水平与反向重复序列之间的距离和同源性相关,并且在不同组织中有所不同。通过RNA编辑靶向的RNA介导的RNA双链体在分子内形成,而由于分子间碱基配对的编辑似乎可以忽略不计。我们目前的证据表明,这些编辑事件可以导致转录后的创建或消除剪接信号影响选择性剪接的外显子。分析表明,重复元件的修饰是RNA编辑的主要活动,对细胞基因表达具有重要意义。对人类RNA的计算分析已经确定了1,445个转录本主要在非编码Alu重复序列内编辑,具有调节可变剪接的潜在作用
RNA editing by adenosine deamination generates RNA and protein diversity through the posttranscriptional modification of single nucleotides in RNA sequences. Few mammalian A-to-I edited genes have been identified despite evidence that many more should exist. Here we identify intramolecular pairs of Alu elements as a major target for editing in the human transcriptome. An experimental demonstration in 43 genes was extended by a broader computational analysis of more than 100,000 human mRNAs. We find that 1,445 human mRNAs (1.4%) are subject to RNA editing at more than 14,500 sites, and our data further suggest that the vast majority of pre-mRNAs (greater than 85%) are targeted in introns by the editing machinery. The editing levels of Alu-containing mRNAs correlate with distance and homology between inverted repeats and vary in different tissues. Alu-mediated RNA duplexes targeted by RNA editing are formed intramolecularly, whereas editing due to intermolecular base-pairing appears to be negligible. We present evidence that these editing events can lead to the posttranscriptional creation or elimination of splice signals affecting alternatively spliced Alu-derived exons. The analysis suggests that modification of repetitive elements is a predominant activity for RNA editing with significant implications for cellular gene expression. A computational analysis of human RNA has identified 1,445 transcripts are edited mainly within non-coding Alu repeats, with the potential effect of regulating alternative splicing
DOI: 10.1016/j.tig.2003.11.001
发表时间: 2004-01-01
期刊: TRENDS IN GENETICS
影响因子: 11.4
作者:
Kreahling, J;Graveley, BR
通讯作者: Graveley, BR
DOI: 10.1126/science.1082588
发表时间: 2003-05-23
期刊: SCIENCE
影响因子: 56.9
作者:
Lev-Maor, G;Sorek, R;Ast, G
通讯作者: Ast, G
DOI: 10.1073/pnas.052692099
发表时间: 2002-03-05
影响因子: 11.1
作者:
Chen, CF;Gentles, AJ;Karlin, S
通讯作者: Karlin, S
DOI: 10.1016/s0968-0004(98)01285-7
发表时间: 1998-10-01
影响因子: 13.8
作者:
Jeanmougin, F;Thompson, JD;Gibson, TJ
通讯作者: Gibson, TJ
DOI: 10.1126/science.1086763
发表时间: 2003-08-08
期刊: SCIENCE
影响因子: 56.9
作者:
Hoopengardner, B;Bhalla, T;Reenan, R
通讯作者: Reenan, R