title: Identification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes.
abstract: Telomeric RNAs (TERRAs) are UUAGGG repeat-containing RNAs that are transcribed from the subtelomere towards the telomere. The precise genomic origin of TERRA has remained elusive. Using a whole-genome RNA-sequencing approach, we identify novel mouse transcripts arising mainly from the subtelomere of chromosome 18, and to a lesser extend chromosome 9, that resemble TERRA in several key aspects. Those transcripts contain UUAGGG-repeats and are heterogeneous in size, fluctuate in abundance in a TERRA-like manner during the cell cycle, are bound by TERRA RNA-binding proteins and are regulated in a manner similar to TERRA in response to stress and the induction of pluripotency. These transcripts are also found to associate with nearly all chromosome ends and downregulation of the transcripts that originate from chromosome 18 causes a reduction in TERRA abundance. Interestingly, downregulation of either chromosome 18 transcripts or TERRA results in increased number of telomere dysfunction-induced foci, suggesting a protective role at telomeres.
authors.affiliation: Telomeres and Telomerase Group, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029 Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: López de Silanes
authors.affiliation: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029 Madrid, Spain.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Graña
authors.affiliation: Telomeres and Telomerase Group, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029 Madrid, Spain.
authors.forename: Maria Luigia
authors.initials: ML
authors.lastname: De Bonis
authors.affiliation: Genomics Unit, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029 Madrid, Spain.
authors.forename: Orlando
authors.initials: O
authors.lastname: Dominguez
authors.affiliation: Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029 Madrid, Spain.
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.affiliation: Telomeres and Telomerase Group, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro, 3, 28029 Madrid, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000737:chemistry* / Q000378:metabolism; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D056426:Genetic Loci; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D017404:In Situ Hybridization, Fluorescence; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D061251:Primary Cell Culture; D011485:Protein Binding; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D008156:Luciferases