Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that are critical in post-transcriptional regulation. Macaca mulatta is an important nonhuman primate that is often used in basic and translational researches. However, the annotation of miRNAs in Macaca mulatta is far from complete, and there are no reports of miRNA editing events in Macaca mulatta, although editing may affect the biogenesis or functions of the miRNAs. To improve miRNA annotation and to reveal editing events of miRNAs in Macaca mulatta, we generated 12 small RNA profiles from eight tissues and performed comprehensive analysis of these profiles. We identified 479 conserved pre-miRNAs that have not been reported in Macaca mulatta and 17 species specific miRNAs. Furthermore, we identified 3386 editing sites with significant editing levels from 471 pre-miRNAs after analyzing the 12 self-generated and 58 additional published sRNA-seq profiles from 17 different types of organs or tissues. In addition to 16 conserved A-to-I editing sites, we identified five conserved C-to-U editing sites in miRNAs of Macaca mulatta and Homo sapiens. We also identified 11 SNPs in the miRNAs of Macaca mulatta. The analysis of the potential targets of 69 miRNAs with editing or mutation events in their seed regions suggest that these editing or mutation events severely changed their targets and their potential functions. These results significantly increase our understanding of miRNAs and their mutation/editing events in Macaca mulatta.

Highlights

  • MicroRNAs are small non-coding RNAs with about 22 nucleotides that could repress their target mRNAs [1]

  • Since the M/E sites in seed regions may change the potential targets of miRNAs, we examined the targets of miRNAs with M/E sites in their seed regions, and the potential functions of the original and edited/mutated miRNAs by analyzing the enriched Gene Ontology (GO) terms and KEGG pathways of their targets

  • After systematically identifying conserved and species specific miRNAs in Macaca mulatta in this study, we identified 479 conserved and 17 species specific pre-miRNAs in this species

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Summary

Introduction

MicroRNAs are small non-coding RNAs with about 22 nucleotides that could repress their target mRNAs [1]. Some miRNAs may be edited in multiple ways during their biogenesis processes [14,15,16,17,18,19,20,21,22,23,24,25,26]. These editing events could either change the nucleotide of mature miRNAs, such as Adenosine-to-Inosine (A-to-I) editing [27], or change the secondary structures of pre-miRNAs and processing of mature miRNAs [26,28,29,30]. Adenosine-to-Inosine (A-to-I) editing is performed by ADAR (adenosine deaminase) on the double-stranded RNAs [14,25] to convert an adenosine residue into an inosine

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