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

Li Guo,Jiafeng Lu,Hailing Li,Zuhong Lu,Qi Yang,Wanjun Gu,Yunfei Bai,Qinyu Ge,Fabio Martelli

doi:10.1371/journal.pone.0021072

Abstract

BackgroundTo 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 FindingsOver 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.ConclusionsThe 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.

Highlights

MicroRNAs, a class of endogenous small non-coding RNAs (,22 nt), play pivotal post-transcriptional regulatory roles in normal physiological functions by targeting messenger RNAs for cleavage or translational repression [1,2,3]
We sequenced the small RNAs of placental samples from pregnant women with mild and severe pre-eclampsia and normal pregnant woman (Table S1)
Similar length distribution patterns were detected across the three samples, different percentages could be found, especially between normal and diseased samples (Figure S1). miRNAs with 39 non-template additional nucleotides were widely detected in the three samples, and adenosine was the most abundant and prevalent additional nucleotide (Figure 1)

Summary

Introduction

MicroRNAs (miRNAs), a class of endogenous small non-coding RNAs (,22 nt), play pivotal post-transcriptional regulatory roles in normal physiological functions by targeting messenger RNAs for cleavage or translational repression [1,2,3]. Recent evidence indicates that miRNA* can be loaded into AGO2 and bind target mRNAs to play a role in regulation network as a potential regulatory molecule [8,9,10,11,12,13]. To gain insight into potential roles of isomiR spectrum and isomiRs with 39 additions in pre-eclampsia, we performed a comprehensive survey of miRNA repertoire and 39 addition events from placental samples with different degrees of pre-eclampsia by applying SOLiD sequencing platform

Methods

Results

Conclusion