Institute for Systems Biology, 1441 N.34th Street, Seattle, WA 98103, USA.
RNA. 2010 Nov;16(11):2170-80. doi: 10.1261/rna.2225110. Epub 2010 Sep 28.
MicroRNAs (miRNAs) have been implicated to play key roles in normal physiological functions, and altered expression of specific miRNAs has been associated with a number of diseases. It is of great interest to understand their roles and a prerequisite for such study is the ability to comprehensively and accurately assess the levels of the entire repertoire of miRNAs in a given sample. It has been shown that some miRNAs frequently have sequence variations termed isomirs. To better understand the extent of miRNA sequence heterogeneity and its potential implications for miRNA function and measurement, we conducted a comprehensive survey of miRNA sequence variations from human and mouse samples using next generation sequencing platforms. Our results suggest that the process of generating this isomir spectrum might not be random and that heterogeneity at the ends of miRNA affects the consistency and accuracy of miRNA level measurement. In addition, we have constructed a database from our sequencing data that catalogs the entire repertoire of miRNA sequences (http://galas.systemsbiology.net/cgi-bin/isomir/find.pl). This enables users to determine the most abundant sequence and the degree of heterogeneity for each individual miRNA species. This information will be useful both to better understand the functions of isomirs and to improve probe or primer design for miRNA detection and measurement.
微小 RNA（miRNAs）在正常生理功能中发挥着关键作用，特定 miRNAs 的表达改变与许多疾病有关。了解它们的作用是非常有趣的，而进行这种研究的前提是能够全面、准确地评估给定样本中整个 miRNA 谱的水平。已经表明，一些 miRNAs 经常具有称为同工型的序列变异。为了更好地理解 miRNA 序列异质性的程度及其对 miRNA 功能和测量的潜在影响，我们使用下一代测序平台对来自人和小鼠样本的 miRNA 序列变异进行了全面调查。我们的结果表明，产生这种同工型谱的过程可能不是随机的，并且 miRNA 末端的异质性会影响 miRNA 水平测量的一致性和准确性。此外，我们已经从测序数据构建了一个数据库，该数据库编目了整个 miRNA 序列库（http://galas.systemsbiology.net/cgi-bin/isomir/find.pl）。这使用户能够确定每个 miRNA 物种的最丰富序列和异质性程度。这些信息对于更好地理解同工型的功能以及改进 miRNA 检测和测量的探针或引物设计都将非常有用。
