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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Genomic positional conservation identifies topological anchor point RNAs linked to developmental loci

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Autor(es):
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Amaral, Paulo P. [1] ; Leonardi, Tommaso [2, 3, 4] ; Han, Namshik [1, 5] ; Vire, Emmanuelle [6] ; Gascoigne, Dennis K. [1] ; Arias-Carrasco, Raul [7] ; Buscher, Magdalena [1] ; Pandolfini, Luca [1] ; Zhang, Anda [8] ; Pluchino, Stefano [2, 3] ; Maracaja-Coutinho, Vinicius [7, 9] ; Nakaya, I, Helder ; Hemberg, Martin [1, 10] ; Shiekhattar, Ramin [8] ; Enright, Anton J. [11] ; Kouzarides, Tony [1]
Número total de Autores: 16
Afiliação do(s) autor(es):
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[1] Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN - England
[2] Univ Cambridge, Dept Clin Neurosci, Cambridge - England
[3] Univ Cambridge, NIHR Biomed Res Ctr, Cambridge - England
[4] European Bioinformat Inst, European Mol Biol Lab, Welcome Genome Campus, Cambridge CB10 1SD - England
[5] Univ Cambridge, Milner Therapeut Inst, Tennis Court Rd, Cambridge CB2 1QN - England
[6] UCL Inst Neurol, MRC Prion Unit, Queen Sq House, Queen Sq, London WC1N 3BG - England
[7] Univ Mayor, Fac Ciencias, Ctr Genom & Bioinformat, Santiago - Chile
[8] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Human Genet, Biomed Res Bldg, Miami, FL 33136 - USA
[9] Univ Chile, Fac Ciencias Quim & Farmaceut, Adv Ctr Chron Dis ACCDiS, Santiago - Chile
[10] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA - England
[11] Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP - England
Número total de Afiliações: 11
Tipo de documento: Artigo Científico
Fonte: Genome Biology; v. 19, MAR 15 2018.
Citações Web of Science: 31
Resumo

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. (AU)

Processo FAPESP: 14/50308-4 - Meta-análise transcricional de RNAs não codificadores longos de posições genômicas conservadas
Beneficiário:Helder Takashi Imoto Nakaya
Linha de fomento: Auxílio à Pesquisa - Regular