Drosha processing controls the specificity and efficiency of global microRNA expression.
Drosha processing controls the specificity and efficiency of global microRNA expression.
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DOI：
10.1016/j.bbagrm.2011.05.015
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发表时间：
2011-11
影响因子：
4.7
通讯作者：
Zeng, Yan
中科院分区：
文献类型：
--
作者：
Feng, Yong;Zhang, Xiaoxiao;Song, Qingfeng;Li, Tongbin;Zeng, Yan
microRNAs（miRNAs）是一个由大约22个核苷酸组成的调控基因表达的大家族。它们首先被转录为长的初级转录物，然后经过一系列加工步骤产生单链成熟的miRNA。在这里，我们发现Drosha在体外以不同的效率切割了数百种人类初级miRNA转录物底物。初级miRNA转录物的差异Drosha易感性与体内相应成熟miRNA的表达显著相关。保守的miRNA在体内表达更有效，并且它们的初级转录物在体外也是更好的Drosha底物。结合二级结构预测和统计分析，我们确定了人类初级miRNA转录本中的特征，这些特征使miRNA在体外易于进行有效的Drosha加工，并在体内更好地表达。我们认为Drosha作用的选择性极大地促进了miRNA生物合成的特异性和效率。此外，这项研究作为一个例子的底物特异性的生化反应调节基因表达在全球范围内在体内。
microRNAs (miRNAs) are a large family of approximately 22-nucleotide-long RNAs that regulate gene expression. They are first transcribed as long, primary transcripts, which then undergo a series of processing steps to generate the single-stranded, mature miRNAs. Here, we showed that Drosha cleaved hundreds of human primary miRNA transcript substrates with different efficiencies in vitro. The differential Drosha susceptibility of the primary miRNA transcripts significantly correlated with the expression of the corresponding, mature miRNAs in vivo. Conserved miRNAs were more efficiently expressed in vivo, and their primary transcripts were also better Drosha substrates in vitro. Combining secondary structure prediction and statistical analyses, we identified features in human primary miRNA transcripts that predisposed miRNAs to efficient Drosha processing in vitro as well as to better expression in vivo. We propose that the selectivity of Drosha action contributes greatly to the specificity and efficiency of miRNA biogenesis. Moreover, this study serves as an example of substrate specificity of a biochemical reaction regulating gene expression at a global scale in vivo.
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