In-Depth Exploration of miRNA: A New Approach to Study miRNA at the miRNA/isomiR Levels
Li Guo, Hui Zhang, Yang Zhao, Sheng Yang and Feng Chen
Affiliation: Department of Epidemiology and Biostatistics and Ministry of Education Key Lab for Modern Toxicology, School of Public Health, Nanjing Medical University, 211166, Nanjing, China.
Keywords: Approach, expression profile, microRNA (miRNA), isomiR.
Accumulating evidences suggest that microRNA (miRNA) is not a single sequence, but a cluster of isomiR
sequences with various 5’/3’ ends and length distributions. The typical analysis always focuses on the annotated canonical
miRNAs, although the multiple isomiRs have been reported as potential regulatory molecules with versatile biological
roles. Herein, we develop an approach to analyze miRNA at the miRNA/isomiR levels. Firstly, isomiR expression profiles
are estimated based on miRNA locus. Secondly, isomiR expression profiles are compared between clustered/homologous
miRNAs. Thirdly, isomiR expression profiles are assessed at the isomiR level. Those isomiRs with the same “seed
sequences” are classified as a special miRNA class. Finally, isomiR:mRNA interaction is predicted at the isomiR level,
and target mRNAs and functional enrichment analysis can be performed to explore biological roles. Furthermore, the
approach is applied to analyze miRNA at the miRNA/isomiR levels using small RNA sequencing datasets of tumor and
normal cells. The analysis at the miRNA/isomiR levels will track miRNA maturation process and biological genesis, and
provide more points to explore versatile biological roles of the small non-coding RNAs.
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