title: Telomeric RNAs are essential to maintain telomeres.
abstract: Telomeres are transcribed generating long non-coding RNAs known as TERRA. Deciphering the role of TERRA has been one of the unsolved issues of telomere biology in the past decade. This has been, in part, due to lack of knowledge on the TERRA loci, thus preventing functional genetic studies. Here, we describe that long non-coding RNAs with TERRA features are transcribed from the human 20q and Xp subtelomeres. Deletion of the 20q locus by using the CRISPR-Cas9 technology causes a dramatic decrease in TERRA levels, while deletion of the Xp locus does not result in decreased TERRA levels. Strikingly, 20q-TERRA ablation leads to dramatic loss of telomere sequences and the induction of a massive DNA damage response. These findings identify chromosome 20q as a main TERRA locus in human cells and represent the first demonstration in any organism of the essential role of TERRA in the maintenance of telomeres.
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Montero
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: López de Silanes
authors.affiliation: Bioinformatics Group, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Graña
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
mesh_terms: D001483:Base Sequence; D064113:CRISPR-Cas Systems / Q000235:genetics; D002460:Cell Line; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D012313:RNA / Q000378:metabolism*; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012313:RNA