Comprehensive analysis of human small RNA sequencing data provides insights into expression profiles and miRNA editing

Abstract

MicroRNAs (miRNAs) play key regulatory roles in various biological processes and diseases. A comprehensive analysis of large scale small RNA sequencing data (smRNA-seq) will be very helpful to explore tissue or disease specific miRNA markers and uncover miRNA variants. Here, we systematically analyzed 410 human smRNA-seq datasets, which samples are from 24 tissue/disease/cell lines. We tested the mapping strategies and found that it was necessary to make multiple-round mappings with different mismatch parameters. miRNA expression profiles revealed that on average ∼70% of known miRNAs were expressed at low level or not expressed (RPM < 1) in a sample and only ∼9% of known miRNAs were relatively highly expressed (RPM > 100). About 30% known miRNAs were not expressed in all of our used samples. The miRNA expression profiles were compiled into an online database (HMED, http://bioinfo.life.hust.edu.cn/smallRNA/). Dozens of tissue/disease specific miRNAs, disease/control dysregulated miRNAs and miRNAs with arm switching events were discovered. Further, we identified some highly confident editing sites including 24 A-to-I sites and 23 C-to-U sites. About half of them were widespread miRNA editing sites in different tissues. We characterized that the 2 types of editing sites have different features with regard to location, editing level and frequency. Our analyses for expression profiles, specific miRNA markers, arm switching, and editing sites, may provide valuable information for further studies of miRNA function and biomarker finding.

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers

“…To ensure the quality of these RNA editing hotspots, we further ruled out the possibility of any unreported SNPs and somatic mutations or cross-mapping (Methods). Among these editing hotspots, 18 (95%) are located at the position 1-8 of mature miRNAs, 12 (63%) have been reported in previous studies (Blow et al 2006;Kawahara et al 2007aKawahara et al ,b, 2008Alon et al 2012;Choudhury et al 2012;Gong et al 2014;Warnefors et al 2014;Saiselet et al 2015;Tomaselli et al 2015;Nishikura 2016), and two editing sites (miR-151a and miR-376a) have been functionally characterized (Kawahara et al 2007a;Choudhury et al 2012). To further characterize these miRNA editing hotspots, we calculated their editing frequency (defined as the fraction of the tumor samples with detectable editing signals), the edited miRNA expression amount (defined as the RPM), and the editing level across cancer types.…”

“…In addition to protein-coding genes, RNA editing can occur in noncoding genes, such as lncRNAs and microRNAs (miRNAs) (Gong et al 2014(Gong et al , 2017. miRNAs are ∼22-nt small RNAs that function in post-transcriptional gene regulation and participate in various cellular pathways and pathological processes, including cancer (Bartel 2004;Garzon et al 2009).…”

“…However, because of the short read length and high similarities among miRNAs, highquality bioinformatic tools for miRNA editing calling were not being developed until very recently (Alon et al 2012Gong et al 2014). As a result, systematic analyses of RNA editing events in miRNAs have been very limited and highly biased toward specific diseases such as glioma (Alon et al 2012;Tomaselli et al 2015).…”

miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells

“…On the other hand, miR-146b-5p is the most highly expressed miRNA in five samples on average and the fourth highest in K562-MVs. It is also highly expressed in The Cancer Genome Atlas acute myelogenous leukemia samples (34) and had a higher expression in acute lymphoblastic leukemia than its controls, according to the HMED database (35).…”

LNCediting: a database for functional effects of RNA editing in lncRNAs

“…Previously, we studied the miRNA expression profiles based on 9566 and 410 human small RNA sequencing data from TCGA and NCBI SRA, respectively (50). Our analysis revealed that the pool of miRNAs was dominated by a small proportion of abundantly expressed miRNAs and ∼70% of known miRNAs were expressed at low level (RPM < 1) or only expressed in specific tissues.…”