Computational identification of biologically functional non-hairpin GC-helices in human Argonaute mRNA

• Published in: BMC bioinformatics Vol. 14; no. 1; p. 122
• Main Authors: Dornseifer, Simon, Sczakiel, Georg
• Format: Journal Article
• Language: English
• Published: London BioMed Central 10.04.2013; BioMed Central Ltd; Springer Nature B.V
• Subjects: 5' Untranslated Regions; Algorithms; Argonaute Proteins - genetics; Base Pairing; Bioinformatics; Biological; Biological research; Biology, Experimental; Biomedical and Life Sciences; Computational Biology/Bioinformatics; Computer Appl. in Life Sciences; Computer programs; GC Rich Sequence; Gene sequencing; Genes; Genetics; Human; Humans; Life Sciences; Messenger RNA; Methods; Microarrays; Plasmids; Protein folding; Proteins; Renilla; Research Article; Ribonucleic acid; Ribonucleic acids; RNA; RNA Folding; RNA sequencing; RNA, Messenger - chemistry; Software; Structural analysis; Studies; Technology application; GC-rich helix; Gene expression; Human argonaute; Non-hairpin; RNA structure
• ISSN: 1471-2105; 1471-2105
• DOI: 10.1186/1471-2105-14-122

Background Perfectly formed duplex elements in RNA occur within folding units, often as a part of hairpin motifs which can be reliably predicted by various RNA folding algorithms. Double helices with consecutive Watson-Crick base-pairing may also be formed between distant RNA segments thereby facilitating long-range interactions of long-chain RNA that may be biologically functional. Here we addressed the potential formation of RNA duplex motifs by long-range RNA-RNA interactions of distantly located matching sequence elements of a single long-chain RNA. Results We generated a Python-based software tool that identifies consecutive RNA duplex elements at any given length and nucleotide content formed by distant sequences. The software tool, dubbed RNAslider , is built on the theoretical RNA structure prediction algorithm Mfold. Source code and sample data sets are available on demand. We found that a small ratio of human genes including the Argonaute (Ago)-like gene family encode mRNAs containing highly GC-rich non-hairpin duplex elements (GC-helix) of equal to or more than 8 base pairs in length and we provide experimental evidence for their biological significance. Conclusion GC-helices are observed preferentially within the 5 ′ -region of mRNAs in an evolutionarily conserved fashion indicating their potential biological role. This view is supported experimentally by post-transcriptional regulation of gene expression of a fusion transcript containing 5 ′ -sequences of human mRNA Ago2 harbouring GC-helices and down-stream coding sequences of Renilla luciferase.