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Long noncoding RNA genes: conservation of sequence and brain expression among diverse amniotes

Rebecca A Chodroff12, Leo Goodstadt3, Tamara M Sirey1, Peter L Oliver3, Kay E Davies13, Eric D Green2, Zoltán Molnár1* and Chris P Ponting13*

Author Affiliations

1 Department of Physiology, Anatomy, and Genetics, Le Gros Clark Building South Parks Road, University of Oxford, Oxford OX1 3QX, UK

2 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Building 50, Room 5222, Bethesda, MD 20892, USA

3 MRC Functional Genomics Unit, Le Gros Clark Building, South Parks Road, University of Oxford, Oxford OX1 3QX, UK

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Genome Biology 2010, 11:R72  doi:10.1186/gb-2010-11-7-r72

Published: 12 July 2010

Abstract

Background

Long considered to be the building block of life, it is now apparent that protein is only one of many functional products generated by the eukaryotic genome. Indeed, more of the human genome is transcribed into noncoding sequence than into protein-coding sequence. Nevertheless, whilst we have developed a deep understanding of the relationships between evolutionary constraint and function for protein-coding sequence, little is known about these relationships for non-coding transcribed sequence. This dearth of information is partially attributable to a lack of established non-protein-coding RNA (ncRNA) orthologs among birds and mammals within sequence and expression databases.

Results

Here, we performed a multi-disciplinary study of four highly conserved and brain-expressed transcripts selected from a list of mouse long intergenic noncoding RNA (lncRNA) loci that generally show pronounced evolutionary constraint within their putative promoter regions and across exon-intron boundaries. We identify some of the first lncRNA orthologs present in birds (chicken), marsupial (opossum), and eutherian mammals (mouse), and investigate whether they exhibit conservation of brain expression. In contrast to conventional protein-coding genes, the sequences, transcriptional start sites, exon structures, and lengths for these non-coding genes are all highly variable.

Conclusions

The biological relevance of lncRNAs would be highly questionable if they were limited to closely related phyla. Instead, their preservation across diverse amniotes, their apparent conservation in exon structure, and similarities in their pattern of brain expression during embryonic and early postnatal stages together indicate that these are functional RNA molecules, of which some have roles in vertebrate brain development.