Feng Yong, Zhang Xiaoxiao, Song Qingfeng, Li Tongbin, Zeng Yan
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Biochim Biophys Acta. 2011 Nov-Dec;1809(11-12):700-7. doi: 10.1016/j.bbagrm.2011.05.015. Epub 2011 Jun 13.
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. This article is part of a Special Issue entitled: MicroRNA's in viral gene regulation.
微小RNA（miRNA）是一个大家族，由大约22个核苷酸长的RNA组成，可调节基因表达。它们最初转录成长链初级转录本，然后经过一系列加工步骤生成单链成熟miRNA。在此，我们表明Drosha在体外以不同效率切割数百种人类初级miRNA转录本底物。初级miRNA转录本对Drosha的不同敏感性与体内相应成熟miRNA的表达显著相关。保守的miRNA在体内表达更高效，其初级转录本在体外也是更好的Drosha底物。结合二级结构预测和统计分析，我们在人类初级miRNA转录本中鉴定出一些特征，这些特征使miRNA在体外易于被Drosha有效加工，并在体内具有更好的表达。我们认为Drosha作用的选择性对miRNA生物合成的特异性和效率有很大贡献。此外，本研究是一个在体内全局范围内调节基因表达的生化反应底物特异性的例子。本文是名为：病毒基因调控中的微小RNA 的特刊的一部分。
