A Comprehensive Survey of miRNA Repertoire and 3′ Addition Events in the Placentas of Patients with Pre-Eclampsia from High-Throughput Sequencing

BACKGROUND: To gain insight into potential roles of isomiR spectrum and isomiRs with 3′ additions in pre-eclampsia, we performed a comprehensive survey of miRNA repertoire and 3′ addition events from placental samples with different degrees of pre-eclampsia by applying SOLiD sequencing platform. PRINCIPAL FINDINGS: Over 30% isomiRs were detected with 3′ non-template additional nucleotides, especially for additional nucleotide of adenosine. However, these modified isomiRs showed a lower percentage of total miRNA expression (<15%). Generally, 1-3 abundant isomiRs from a given miRNA locus were identified, but none of them was detected with 3′ additions. Different miRNAs indicated various isomiR spectrums and expression patterns. The most abundant isomiR spectrum, isomiR profile and expression pattern always were stability, but herein we found several exceptions across samples, especially between normal and diseased samples. At isomiR level, we detected a distinct subset of differentially expressed modified isomiRs between normal and diseased samples or between mild and severe samples. Gene Ontology analysis of their experimentally validated target genes revealed enrichment for specific biological process categories. CONCLUSIONS: The phenomenon of multiple isomiRs, especially for isomiRs with 3′ additions, is not a random event during pre-miRNA processing. Varieties of isomiRs and expression patterns reveal potential functional implication and should be taken into account. The study enriches association of miRNAs and human disease, including potential roles of various miRNA variants and 3′ addition events.