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This article is part of the supplement: Italian Society of Bioinformatics (BITS): Annual Meeting 2012

Open Access Research

Examples of sequence conservation analyses capture a subset of mouse long non-coding RNAs sharing homology with fish conserved genomic elements

Swaraj Basu1, Ferenc Müller2 and Remo Sanges1*

Author Affiliations

1 Laboratory of Animal Physiology and Evolution, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121, Naples, Italy

2 Centre for Rare Diseases and Personalized Medicine, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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BMC Bioinformatics 2013, 14(Suppl 7):S14  doi:10.1186/1471-2105-14-S7-S14

Published: 22 April 2013

Abstract

Background

Long non-coding RNAs (lncRNA) are a major class of non-coding RNAs. They are involved in diverse intra-cellular mechanisms like molecular scaffolding, splicing and DNA methylation. Through these mechanisms they are reported to play a role in cellular differentiation and development. They show an enriched expression in the brain where they are implicated in maintaining cellular identity, homeostasis, stress responses and plasticity. Low sequence conservation and lack of functional annotations make it difficult to identify homologs of mammalian lncRNAs in other vertebrates. A computational evaluation of the lncRNAs through systematic conservation analyses of both sequences as well as their genomic architecture is required.

Results

Our results show that a subset of mouse candidate lncRNAs could be distinguished from random sequences based on their alignment with zebrafish phastCons elements. Using ROC analyses we were able to define a measure to select significantly conserved lncRNAs. Indeed, starting from ~2,800 mouse lncRNAs we could predict that between 4 and 11% present conserved sequence fragments in fish genomes. Gene ontology (GO) enrichment analyses of protein coding genes, proximal to the region of conservation, in both organisms highlighted similar GO classes like regulation of transcription and central nervous system development. The proximal coding genes in both the species show enrichment of their expression in brain. In summary, we show that interesting genomic regions in zebrafish could be marked based on their sequence homology to a mouse lncRNA, overlap with ESTs and proximity to genes involved in nervous system development.

Conclusions

Conservation at the sequence level can identify a subset of putative lncRNA orthologs. The similar protein-coding neighborhood and transcriptional information about the conserved candidates provide support to the hypothesis that they share functional homology. The pipeline herein presented represents a proof of principle showing that a portion between 4 and 11% of lncRNAs retains region of conservation between mammals and fishes. We believe this study will result useful as a reference to analyze the conservation of lncRNAs in newly sequenced genomes and transcriptomes.