Global Analysis of RNA Secondary Structure in Two Metazoans

SummaryThe secondary structure of RNA is necessary for its maturation, regulation, processing, and function. However, the global influence of RNA folding in eukaryotes is still unclear. Here, we use a high-throughput, sequencing-based, structure-mapping approach to identify the paired (double-stranded RNA [dsRNA]) and unpaired (single-stranded RNA [ssRNA]) components of the Drosophila melanogaster and Caenorhabditis elegans transcriptomes, which allows us to identify conserved features of RNA secondary structure in metazoans. From this analysis, we find that ssRNAs and dsRNAs are significantly correlated with specific epigenetic modifications. Additionally, we find key structural patterns across protein-coding transcripts that indicate that RNA folding demarcates regions of protein translation and likely affects microRNA-mediated regulation of mRNAs in animals. Finally, we identify and characterize 546 mRNAs whose folding pattern is significantly correlated between these metazoans, suggesting that their structure has some function. Overall, our findings provide a global assessment of RNA folding in animals.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► RNA folding in miRNA target sites is distinct between animals ► There is a negative correlation between miRNA target-site structure and miRISC binding ► Conserved secondary structure features demarcate protein-coding regions of animal mRNAs ► There are conserved features of RNA secondary structure in animals