Frequency and fate of microRNA editing in human brain.
Frequency and fate of microRNA editing in human brain.
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DOI：
10.1093/nar/gkn479
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发表时间：
2008-09
影响因子：
14.9
通讯作者：
Nishikura, Kazuko
中科院分区：
文献类型：
--
作者：
Kawahara, Yukio;Megraw, Molly;Kreider, Edward;Iizasa, Hisashi;Valente, Louis;Hatzigeorgiou, Artemis G.;Nishikura, Kazuko
某些 microRNA (miRNA) 基因 (pri-miRNA) 的初级转录物会受到 RNA 编辑的影响，将腺苷转化为肌苷（A→I RNA 编辑）。然而，pri-miRNA 编辑的频率和编辑后的 pri-miRNA 的命运在很大程度上仍有待确定。对已知 pri-miRNA 编辑位点的检查表明，UAG 三联体序列的腺苷残基可能被更频繁地编辑。因此，在本研究中，我们对包含 UAG 三联体序列的人类 pri-miRNA 进行了大规模调查。通过对 pri-miRNA 对应的 RT-PCR 产物进行直接测序，我们检查了 209 个 pri-miRNA，并在 47 个 pri-miRNA 中鉴定了 43 个 UAG 和 43 个非 UAG 编辑位点，这些编辑位点在人脑中被高度编辑。使用重组 Drosha-DGCR8 和 Dicer-TRBP（人类免疫缺陷病毒反式激活反应 RNA 结合蛋白）复合物进行的体外 miRNA 加工测定表明，大多数 pri-miRNA 编辑可能会干扰 miRNA 加工步骤。此外，通过对将从编辑的 pri-miRNA 加工而来的 miRNA 进行靶向克隆和测序，鉴定出四种具有改变的种子序列的新编辑的 miRNA。我们的研究预测~16%的人类pri-miRNA会受到A→I编辑，因此，miRNA编辑可能对miRNA介导的基因沉默产生很大影响。
Primary transcripts of certain microRNA (miRNA) genes (pri-miRNAs) are subject to RNA editing that converts adenosine to inosine (A→I RNA editing). However, the frequency of the pri-miRNA editing and the fate of edited pri-miRNAs remain largely to be determined. Examination of already known pri-miRNA editing sites indicated that adenosine residues of the UAG triplet sequence might be edited more frequently. In the present study, therefore, we conducted a large-scale survey of human pri-miRNAs containing the UAG triplet sequence. By direct sequencing of RT–PCR products corresponding to pri-miRNAs, we examined 209 pri-miRNAs and identified 43 UAG and also 43 non-UAG editing sites in 47 pri-miRNAs, which were highly edited in human brain. In vitro miRNA processing assay using recombinant Drosha-DGCR8 and Dicer-TRBP (the human immuno deficiency virus transactivating response RNA-binding protein) complexes revealed that a majority of pri-miRNA editing is likely to interfere with the miRNA processing steps. In addition, four new edited miRNAs with altered seed sequences were identified by targeted cloning and sequencing of the miRNAs that would be processed from edited pri-miRNAs. Our studies predict that ∼16% of human pri-miRNAs are subject to A→I editing and, thus, miRNA editing could have a large impact on the miRNA-mediated gene silencing.
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影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
11.4
作者：
Eisenberg, E;Nemzer, S;Levanon, EY
通讯作者：
Levanon, EY
影响因子：
64.8
作者：
Burns, CM;Chu, H;Emeson, RB
通讯作者：
Emeson, RB
影响因子：
56.9
作者：
Hoopengardner, B;Bhalla, T;Reenan, R
通讯作者：
Reenan, R
影响因子：
12.3
作者：
Blow MJ;Grocock RJ;van Dongen S;Enright AJ;Dicks E;Futreal PA;Wooster R;Stratton MR
通讯作者：
Stratton MR