Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Department of Applied Chemistry, Kyung Hee University, Yongin, Gyeonggi 17104, South Korea 3.
Genome Res. 2017 Oct;27(10):1769-1781. doi: 10.1101/gr.222067.117. Epub 2017 Sep 6.
MicroRNAs are short RNAs that serve as regulators of gene expression and are essential components of normal development as well as modulators of disease. MicroRNAs generally act cell-autonomously, and thus their localization to specific cell types is needed to guide our understanding of microRNA activity. Current tissue-level data have caused considerable confusion, and comprehensive cell-level data do not yet exist. Here, we establish the landscape of human cell-specific microRNA expression. This project evaluated 8 billion small RNA-seq reads from 46 primary cell types, 42 cancer or immortalized cell lines, and 26 tissues. It identified both specific and ubiquitous patterns of expression that strongly correlate with adjacent superenhancer activity. Analysis of unaligned RNA reads uncovered 207 unknown minor strand (passenger) microRNAs of known microRNA loci and 495 novel putative microRNA loci. Although cancer cell lines generally recapitulated the expression patterns of matched primary cells, their isomiR sequence families exhibited increased disorder, suggesting DROSHA- and DICER1-dependent microRNA processing variability. Cell-specific patterns of microRNA expression were used to de-convolute variable cellular composition of colon and adipose tissue samples, highlighting one use of these cell-specific microRNA expression data. Characterization of cellular microRNA expression across a wide variety of cell types provides a new understanding of this critical regulatory RNA species.
微小 RNA 是一种短的 RNA，作为基因表达的调节剂，是正常发育的重要组成部分，也是疾病的调节剂。微小 RNA 通常自主发挥作用，因此需要将其定位到特定的细胞类型，以指导我们对微小 RNA 活性的理解。目前的组织水平数据引起了相当大的混乱，而且还没有全面的细胞水平数据。在这里，我们建立了人类细胞特异性微小 RNA 表达的全景。该项目评估了来自 46 种原代细胞类型、42 种癌症或永生化细胞系和 26 种组织的 40 亿个小 RNA-seq 读取。它确定了与相邻超级增强子活性强烈相关的特异性和普遍表达模式。对未对齐的 RNA 读取的分析揭示了 207 个已知微小 RNA 基因座的未知次要链（过客）微小 RNA 和 495 个新的假定微小 RNA 基因座。尽管癌细胞系通常再现了匹配的原代细胞的表达模式，但它们的 isomiR 序列家族表现出增加的无序性，这表明 DROSHA 和 DICER1 依赖性微小 RNA 加工的可变性。微小 RNA 表达的细胞特异性模式用于反卷积结肠和脂肪组织样本中可变的细胞组成，突出了这些细胞特异性微小 RNA 表达数据的一个用途。对广泛的细胞类型中细胞微小 RNA 表达的特征描述提供了对这种关键调节性 RNA 物种的新认识。
