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

Chodroff RA, Goodstadt L, Sirey TM, Oliver PL, Davies KE, Green ED, Molnár Z, Ponting CP - Genome Biol. (2010)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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

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.

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Conservation of lncRNA expression in developing avian and mammalian brains. (a-c) Digoxigenin-labeled riboprobes complementary to lncRNAs AK043754 (a), AK082072 (b), and AK082467 (c) were hybridized to chicken (E4, 6, 8,12), opossum (P12, 20), and mouse (E13, 15, 17, 18 and P0) brain sections. (a) AK043754: strong hybridization seen in the germinal zone of the telencephalic cortex at early developmental time points (red arrowheads) and then concentrated within the piriform (olfactory) cortex at later stages (black arrowheads). (b) AK082072: hybridization signals seen in the stria terminalis (red arrowheads) and the telencephalic ventricular zone (green arrowheads). Signal was undetectable at later developmental stages. (c) AK082467: hybridization signals seen in the ventricular zone of the hippocampal formation (green arrowheads), the preoptic area of the hypothalamus (red arrowheads), and the epithalamus (black arrowheads). Signal was undetectable at later developmental stages. Scale bars = 200 μm.
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Figure 6: Conservation of lncRNA expression in developing avian and mammalian brains. (a-c) Digoxigenin-labeled riboprobes complementary to lncRNAs AK043754 (a), AK082072 (b), and AK082467 (c) were hybridized to chicken (E4, 6, 8,12), opossum (P12, 20), and mouse (E13, 15, 17, 18 and P0) brain sections. (a) AK043754: strong hybridization seen in the germinal zone of the telencephalic cortex at early developmental time points (red arrowheads) and then concentrated within the piriform (olfactory) cortex at later stages (black arrowheads). (b) AK082072: hybridization signals seen in the stria terminalis (red arrowheads) and the telencephalic ventricular zone (green arrowheads). Signal was undetectable at later developmental stages. (c) AK082467: hybridization signals seen in the ventricular zone of the hippocampal formation (green arrowheads), the preoptic area of the hypothalamus (red arrowheads), and the epithalamus (black arrowheads). Signal was undetectable at later developmental stages. Scale bars = 200 μm.

Mentions: Probes specific to chicken, opossum, and mouse AK043754 orthologs hybridize to the germinal zone of the telencephalic cortex in coronal and sagittal sections of early developmental brain in all three species (red arrowheads in Figure 6a). While the neuroanatomical homology relationships between mammalian and avian brains remain controversial (see [46] for a review), most researchers agree that the telencephalic germinal zone is a source of neural progenitors in both mammals and birds [48]. We found that AK043754-expressing cells appear to migrate radially away from the ventricular germinal zone to the pial surface as development progresses in all three species. At later developmental stages (E12, P20, and P0 in chicken, opossum, and mouse, respectively), AK043754 is expressed within the piriform (olfactory) cortex (black arrowheads in Figure 6a). This conserved expression pattern - from the telencephalic germinal zone to a specific cortical substructure - implies negative selection acting on as yet unidentified AK043754 regulatory elements.


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

Chodroff RA, Goodstadt L, Sirey TM, Oliver PL, Davies KE, Green ED, Molnár Z, Ponting CP - Genome Biol. (2010)

Conservation of lncRNA expression in developing avian and mammalian brains. (a-c) Digoxigenin-labeled riboprobes complementary to lncRNAs AK043754 (a), AK082072 (b), and AK082467 (c) were hybridized to chicken (E4, 6, 8,12), opossum (P12, 20), and mouse (E13, 15, 17, 18 and P0) brain sections. (a) AK043754: strong hybridization seen in the germinal zone of the telencephalic cortex at early developmental time points (red arrowheads) and then concentrated within the piriform (olfactory) cortex at later stages (black arrowheads). (b) AK082072: hybridization signals seen in the stria terminalis (red arrowheads) and the telencephalic ventricular zone (green arrowheads). Signal was undetectable at later developmental stages. (c) AK082467: hybridization signals seen in the ventricular zone of the hippocampal formation (green arrowheads), the preoptic area of the hypothalamus (red arrowheads), and the epithalamus (black arrowheads). Signal was undetectable at later developmental stages. Scale bars = 200 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2926783&req=5

Figure 6: Conservation of lncRNA expression in developing avian and mammalian brains. (a-c) Digoxigenin-labeled riboprobes complementary to lncRNAs AK043754 (a), AK082072 (b), and AK082467 (c) were hybridized to chicken (E4, 6, 8,12), opossum (P12, 20), and mouse (E13, 15, 17, 18 and P0) brain sections. (a) AK043754: strong hybridization seen in the germinal zone of the telencephalic cortex at early developmental time points (red arrowheads) and then concentrated within the piriform (olfactory) cortex at later stages (black arrowheads). (b) AK082072: hybridization signals seen in the stria terminalis (red arrowheads) and the telencephalic ventricular zone (green arrowheads). Signal was undetectable at later developmental stages. (c) AK082467: hybridization signals seen in the ventricular zone of the hippocampal formation (green arrowheads), the preoptic area of the hypothalamus (red arrowheads), and the epithalamus (black arrowheads). Signal was undetectable at later developmental stages. Scale bars = 200 μm.
Mentions: Probes specific to chicken, opossum, and mouse AK043754 orthologs hybridize to the germinal zone of the telencephalic cortex in coronal and sagittal sections of early developmental brain in all three species (red arrowheads in Figure 6a). While the neuroanatomical homology relationships between mammalian and avian brains remain controversial (see [46] for a review), most researchers agree that the telencephalic germinal zone is a source of neural progenitors in both mammals and birds [48]. We found that AK043754-expressing cells appear to migrate radially away from the ventricular germinal zone to the pial surface as development progresses in all three species. At later developmental stages (E12, P20, and P0 in chicken, opossum, and mouse, respectively), AK043754 is expressed within the piriform (olfactory) cortex (black arrowheads in Figure 6a). This conserved expression pattern - from the telencephalic germinal zone to a specific cortical substructure - implies negative selection acting on as yet unidentified AK043754 regulatory elements.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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

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.

Show MeSH
Related in: MedlinePlus