Telomeric RNAs are essential to maintain telomeres

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...

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Detalles Bibliográficos
Autores: Montero Valderrama, Juan Jose, Lopez de Silanes, Isabel, Graña Castro, Osvaldo, Blasco , MA
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7873
Acceso en línea:http://hdl.handle.net/20.500.12105/7873
Access Level:acceso abierto
Palabra clave:Base Sequence
CRISPR-Cas Systems
Cell Line
Chromosomes, Human, Pair 20
Chromosomes, Human, X
Genetic Loci
Genotype
Humans
RNA
RNA, Long Noncoding
RNA, Messenger
Sequence Deletion
Telomere
Telomere Homeostasis
Descripción
Sumario: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.