Adenosine deamination in human transcripts generates novel microRNA binding sites.
Adenosine deamination in human transcripts generates novel microRNA binding sites.
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DOI：
10.1093/hmg/ddp443
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发表时间：
2009-12-15
影响因子：
3.5
通讯作者：
Davidson BL
中科院分区：
文献类型：
--
作者：
Borchert GM;Gilmore BL;Spengler RM;Xing Y;Lanier W;Bhattacharya D;Davidson BL
动物在多个水平上调节基因表达，从而增加了蛋白质组的复杂性。这些调控事件包括由小的非编码RNA（例如microRNA）介导的转录后基因沉默，以及由作用于双链RNA的腺苷脱氨酶（阿达尔）产生的腺苷至肌苷（A-to-I）编辑。最近的数据表明，这些监管过程在根本层面上是相互关联的。A-to-I编辑可以影响Drosha加工或直接改变负责mRNA靶向的microRNA（miRNA）序列。在这里，我们分析了先前报道的人类cDNA中发生的腺苷脱氨，并询问mRNA 3′非翻译区（UTR）中的A至I编辑事件与mRNA：miRNA结合之间是否存在关系。我们发现A-to-I编辑与miRNA互补性变化之间存在显著相关性。总之，在评估的12723个不同的腺苷脱氨基中，发现超过3000个与人类miRNA的子集形成7聚体互补（称为种子匹配）。在200个EST中，我们还注意到在特定的13个核苷酸基序内进行编辑。引人注目的是，该基序的脱氨基作用同时产生了与三种（否则不相关的）miRNA的种子匹配。我们的研究结果表明，作为阿达尔活性的一种新功能的miRNA调控位点的创建。因此，许多miRNA靶位点只能通过检查表达的序列来鉴定。
Animals regulate gene expression at multiple levels, contributing to the complexity of the proteome. Among these regulatory events are post-transcriptional gene silencing, mediated by small non-coding RNAs (e.g. microRNAs), and adenosine-to-inosine (A-to-I) editing, generated by adenosine deaminases that act on double-stranded RNA (ADAR). Recent data suggest that these regulatory processes are connected at a fundamental level. A-to-I editing can affect Drosha processing or directly alter the microRNA (miRNA) sequences responsible for mRNA targeting. Here, we analyzed the previously reported adenosine deaminations occurring in human cDNAs, and asked if there was a relationship between A-to-I editing events in the mRNA 3′ untranslated regions (UTRs) and mRNA:miRNA binding. We find significant correlations between A-to-I editing and changes in miRNA complementarities. In all, over 3000 of the 12 723 distinct adenosine deaminations assessed were found to form 7-mer complementarities (known as seed matches) to a subset of human miRNAs. In 200 of the ESTs, we also noted editing within a specific 13 nucleotide motif. Strikingly, deamination of this motif simultaneously creates seed matches to three (otherwise unrelated) miRNAs. Our results suggest the creation of miRNA regulatory sites as a novel function for ADAR activity. Consequently, many miRNA target sites may only be identifiable through examining expressed sequences.
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影响因子：
14.9
作者：
Wheeler, David L.;Barrett, Tanya;Yaschenko, Eugene
通讯作者：
Yaschenko, Eugene
影响因子：
64.8
作者：
Burns, CM;Chu, H;Emeson, RB
通讯作者：
Emeson, RB
影响因子：
4.5
作者：
Osenberg, Sivan;Dominissini, Dan;Eisenberg, Eli
通讯作者：
Eisenberg, Eli
DOI：
10.1016/0005-2787(68)90371-7
发表时间：
1968-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
YOSHIDA, M;KAZIRO, Y;UKITA, T
通讯作者：
UKITA, T
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB