A-to-I editing in the miRNA seed region regulates target mRNA selection and silencing efficiency.
A-to-I editing in the miRNA seed region regulates target mRNA selection and silencing efficiency.
复制标题
DOI：
10.1093/nar/gku662
复制
发表时间：
2014-09
影响因子：
14.9
通讯作者：
Ui-Tei K
中科院分区：
文献类型：
--
作者：
Kume H;Hino K;Galipon J;Ui-Tei K
腺苷脱氨酶作用于RNA(ADARs)是一种转录后修饰，导致基因组DNA与转录后的RNA序列不一致，从而导致转录组的多样性。肌苷优先与胞苷形成碱基对，这意味着通过蛋白质编码机制，可以观察到mRNA序列中的A-to-I修饰为A-to-G替换。全基因组研究表明，大多数编辑事件发生在非编码的RNA序列中，但人们对其功能意义知之甚少。MiRNAs是一种小的非编码RNA，调节靶mRNAs的表达，与其种子区域具有互补性。在这里，我们证实了在miRNA种子双链中的A-to-I编辑在体内全局地重新分配了他们的靶mRNAs，并揭示了在种子区域含有肌苷的miRNA与在相同位置含有鸟苷的相应miRNA相比显示出不同程度的沉默效率。通过熔化温度测量得出的碱基配对稳定性的差异，在含有C：G或I：C对的种子-靶双链之间可能解释了观察到的沉默效率。这些发现明确地表明，就miRNAs调节基因表达而言，C：G和I：C对在生物学上是不同的。
Hydrolytic deamination of adenosine to inosine (A-to-I) by adenosine deaminases acting on RNA (ADARs) is a post-transcriptional modification which results in a discrepancy between genomic DNA and the transcribed RNA sequence, thus contributing to the diversity of the transcriptome. Inosine preferentially base pairs with cytidine, meaning that A-to-I modifications in the mRNA sequences may be observed as A-to-G substitutions by the protein-coding machinery. Genome-wide studies have revealed that the majority of editing events occur in non-coding RNA sequences, but little is known about their functional meaning. MiRNAs are small non-coding RNAs that regulate the expression of target mRNAs with complementarities to their seed region. Here, we confirm that A-to-I editing in the miRNA seed duplex globally reassigns their target mRNAs in vivo, and reveal that miRNA containing inosine in the seed region exhibits a different degree of silencing efficiency compared to the corresponding miRNA with guanosine at the same position. The difference in base-pairing stability, deduced by melting temperature measurements, between seed-target duplexes containing either C:G or I:C pairs may account for the observed silencing efficiency. These findings unequivocally show that C:G and I:C pairs are biologically different in terms of gene expression regulation by miRNAs.
登录
查看更多内容
影响因子：
46.9
作者：
Jackson, AL;Bartz, SR;Linsley, PS
通讯作者：
Linsley, PS
影响因子：
4.4
作者：
Linsen SE;de Wit E;de Bruijn E;Cuppen E
通讯作者：
Cuppen E
影响因子：
7
作者：
Berezikov, Eugene;Robine, Nicolas;Lai, Eric C.
通讯作者：
Lai, Eric C.
影响因子：
64.8
作者：
Burns, CM;Chu, H;Emeson, RB
通讯作者：
Emeson, RB
影响因子：
4.8
作者：
Iizasa, Hisashi;Wulff, Bjorn-Erik;Nishikura, Kazuko
通讯作者：
Nishikura, Kazuko