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.
Highlights
Telomeres are transcribed generating long non-coding RNAs known as TERRA
A number of subtelomeric transcripts identified in samples that underwent UUAGGG-transcript enrichment have been recently proposed to represent the human TERRA transcriptome, further confirmation that these transcripts had TERRA features was lacking[13]
Eighteen different human subtelomeres were proposed to contain TERRA loci, the authors did not study whether these transcripts had TERRA features[13]
Summary
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. 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. TERRA transcripts are nuclear long non-coding RNAs that are transcribed from the subtelomere towards the telomere[1,2] They are transcribed by RNA polymerase II, giving rise to transcripts that contain UUAGGG-repeats, being the presence of this repeat their main features. They are heterogeneous in size (0.2–10 kb in humans and mice) as indicated by the smear detected in TERRA northern blots[1,2]. These unprecedented findings demonstrate that TERRA transcripts are essential for the maintenance of a functional telomere cap
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