An integrated expression atlas of miRNAs and their promoters in human and mouse

MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. We created the first integrated expression atlas of miRNAs and their promoters in mammalian cells by deep sequencing matched short RNA (sRNA) and Cap Analysis Gene Expression (CAGE) libraries from 492 RNA samples. Most samples were derived from human primary cells, allowing us to annotate each human miRNA by its sRNA expression profile across primary cell types. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species, reflecting the importance of transcriptional regulation of miRNA expression. As primary and mature miRNA expression levels in the matched libraries were correlated, CAGE expression of primary miRNAs could be used as a proxy for the expression level of mature miRNAs, allowing us to extend the miRNA expression survey to the 1,829 human and 1,029 mouse CAGE libraries in FANTOM5. We thus provide the first broad atlas of miRNA expression in primary cells, as well as the largest map of miRNA promoters to date, establishing the foundation for detailed analysis of expression patterns and transcriptional control regions of miRNAs.