Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci.
Authors
Amaral, Paulo P
Viré, Emmanuelle
Gascoigne, Dennis K
Arias-Carrasco, Raúl
Büscher, Magdalena
Zhang, Anda
Maracaja-Coutinho, Vinicius
Nakaya, Helder I
Hemberg, Martin
Shiekhattar, Ramin
Enright, Anton J
Publication Date
2018-03-15Journal Title
Genome Biology
ISSN
1474-7596
Publisher
Springer Nature
Volume
19
Issue
1
Pages
32-32
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Amaral, P. P., Leonardi, T., Han, N., Viré, E., Gascoigne, D. K., Arias-Carrasco, R., Büscher, M., et al. (2018). Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci.. Genome Biology, 19 (1), 32-32. https://doi.org/10.1186/s13059-018-1405-5
Abstract
BACKGROUND: The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality. RESULTS: We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes. These positionally conserved lncRNA genes are primarily associated with developmental transcription factor loci with which they are coexpressed in a tissue-specific manner. Over half of positionally conserved RNAs in this set are linked to chromatin organization structures, overlapping binding sites for the CTCF chromatin organiser and located at chromatin loop anchor points and borders of topologically associating domains (TADs). We define these RNAs as topological anchor point RNAs (tapRNAs). Characterization of these noncoding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other's expression and influence the metastatic phenotype of cancer cells in vitro in a similar fashion. Furthermore, we find that tapRNAs contain conserved sequence domains that are enriched in motifs for zinc finger domain-containing RNA-binding proteins and transcription factors, whose binding sites are found mutated in cancers. CONCLUSIONS: This work leverages positional conservation to identify lncRNAs with potential importance in genome organization, development and disease. The evidence that many developmental transcription factors are physically and functionally connected to lncRNAs represents an exciting stepping-stone to further our understanding of genome regulation.
Keywords
Cancer, Chromatin architecture, Development, Topology, Zinc finger, lncRNAs
Sponsorship
VMC was supported by a PAICONICYT grant (PAI79170021) and a FONDECYT-CONICYT grant (11161020).
Funder references
European Research Council (268569)
Cancer Research Uk (None)
Cancer Research UK (17001)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1186/s13059-018-1405-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/278457
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