Abstract
Long non-coding RNAs (lncRNAs) have been shown to regulate gene expression, chromatin domains and chromosome stability in eukaryotic cells. Recent observations have reported the existence of telomeric repeats containing long ncRNAs – TERRA in mammalian and yeast cells. However, their functions remain poorly characterized. Here, we report the existence in S. cerevisiae of several lncRNAs within Y′ subtelomeric regions. We have called them subTERRA. These belong to Cryptic Unstable Transcripts (CUTs) and Xrn1p-sensitive Unstable Transcripts (XUTs) family. subTERRA transcription, carried out mainly by RNAPII, is initiated within the subtelomeric Y’ element and occurs in both directions, towards telomeres as well as centromeres. We show that subTERRA are distinct from TERRA and are mainly degraded by the general cytoplasmic and nuclear 5′- and 3′- RNA decay pathways in a transcription-dependent manner. subTERRA accumulates preferentially during the G1/S transition and in C-terminal rap1 mutant but independently of Rap1p function in silencing. The accumulation of subTERRA in RNA decay mutants coincides with telomere misregulation: shortening of telomeres, loss of telomeric clustering in mitotic cells and changes in silencing of subtelomeric regions. Our data suggest that subtelomeric RNAs expression links telomere maintenance to RNA degradation pathways.
Highlights
In Saccharomyces cerevisiae, telomeres consist of 350 ± 75 base pairs of C1–3A/TG1–3 DNA and are required for the stable maintenance of chromosomes [1]
NcRNA or ARRET transcribed in opposite direction, both subjected to the nuclear 5′end decay mediated by Rat1p [40,51]
We show that several long, unstable RNAs are produced within the budding yeast subtelomeric Y′ region. We defined these Long non-coding RNAs (lncRNAs) as subTERRA since, contrary to telomeric repeat-containing RNA (TERRA) they do not cover the terminal telomeric repeats. subTERRA are transcribed in both transcriptional senses which gives rise to two sets of RNAs: subTERRA-Cryptic Unstable Transcripts (CUTs), sensitive to nuclear degradation are transcribed towards centromere, and subTERRA-Xrn1p-sensitive Unstable Transcripts (XUTs) are preferentially degraded in the cytoplasm by Xrn1p
Summary
In Saccharomyces cerevisiae, telomeres consist of 350 ± 75 base pairs of C1–3A/TG1–3 DNA and are required for the stable maintenance of chromosomes [1]. This size is kept within a narrow size range, specific for a particular strain and does not change in culture [2]. Simple telomeric C 1-3 A/TG1–3 repeats are followed by two subtelomeric sequences: the X-core and the Y′ [3]. 300 bp) are present in all telomeres and Y′ (long of 6.7 kb or short of 5.2 kb) in about 70% of telomeres. Y′ appears in 1 to 4 tandem copies separated by short tracks of telomeric repeats.
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