Structural basis of microRNA length variety.

Structural basis of microRNA length variety.
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DOI:
10.1093/nar/gkq727
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发表时间:
2011-01
影响因子:
14.9
通讯作者:
Krzyzosiak WJ
Krzyzosiak WJ
中科院分区:
生物学2区
文献类型:
--
作者:
Starega-Roslan J;Krol J;Koscianska E;Kozlowski P;Szlachcic WJ;Sobczak K;Krzyzosiak WJ

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人类微小RNA(miRNAs)的生物发生包括两个RNA切割步骤,其中涉及RNA酶Drosha和Dicer的活性。不同长度的miRNA由不同的基因产生,并且长度异质的miRNA由单个miRNA基因产生。我们确定了许多miRNA前体的溶液结构,并使用一种新的测量方法分析了miRNA长度多样性的结构基础:切割RNA的加权平均长度(WALDI)。我们发现,前体发夹中存在的不对称结构基序是Dicer产生的miRNA长度多样性的主要原因。miRNA及其前体的高分辨率北方印迹显示,不完全特异性的Dicer和Drosha切割均导致miRNA长度异质性。这些发现的相关性的动态切割复合物,mRNA调控的miRNA,RNA干扰和miRNA技术进行了讨论。
The biogenesis of human microRNAs (miRNAs) includes two RNA cleavage steps in which the activities of the RNases Drosha and Dicer are involved. miRNAs of diverse lengths are generated from different genes, and miRNAs that are heterogeneous in length are produced from a single miRNA gene. We determined the solution structures of many miRNA precursors and analysed the structural basis of miRNA length diversity using a new measure: the weighted average length of diced RNA (WALDI). We found that asymmetrical structural motifs present in precursor hairpins are primarily responsible for the length diversity of miRNAs generated by Dicer. High-resolution northern blots of miRNAs and their precursors revealed that both Dicer and Drosha cleavages of imperfect specificity contributed to the miRNA length heterogeneity. The relevance of these findings to the dynamics of the dicing complex, mRNA regulation by miRNA, RNA interference and miRNA technologies are discussed.
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