A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing

MicroRNAs (miRNAs) are small non-coding regulatory RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. In order to identify miRNAs and to assess their expression patterns, we sequenced over 250 small RNA libraries from 26 different organ systems and cell types of human and rodents, enriched in euronal as well as normal and malignant hematopoietic cells and tissues. We present expression profiles derived from clone count data and provide novel computational tools for their analysis. Unexpectedly, a relatively small set of miRNAs, many of which are ubiquitously expressed, account for most of the difference in miRNA profiles between cell lineages and tissues. This broad survey also provides detailed and accurate information about mature sequences, precursors, genome locations, maturation processes, inferred transcriptional units and conservation patterns. We also propose a subclassification scheme for miRNAs for assisting future experimental and computational functional analyses. Keywords: miRNA microarray; expression profiling To validate the results of the miRNA profiling achieved by sequence analysis of small RNA clone libraries we performed additional dual color microarray hybridizations using a synthetic miRNA pool as a common reference. 5 μg total RNA of the samples hsa_Hepatoma-PLC (array # 517063), hsa_Hepatocell-carcinoma-Huh7-mock (array #517064), hsa_Gliobl-SNB19 (array #517065), hsa_Hippocamp-adult (array #517066), and hsa_T-cell-CD4-A301 (array #517067), were hybridized on miRNA arrays carrying probes for all miRNA described in the present study. Sample hsa_T-cell-CD4-A301 was also analysed using 10 μg of total RNA to check for reproducibility and potential bias due to varying amounts of input RNA (array #517068).