Journal ArticleDOI
Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence
Bettina Balk,André Maicher,Martina Dees,Julia Klermund,Sarah Luke-Glaser,Katharina Bender,Brian Luke +6 more
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TLDR
It is shown that RNA-DNA hybrids form at telomeres and are removed by RNase H enzymes in the budding yeast, Saccharomyces cerevisiae, and regulation of TERRA transcription and telomeric RNA- DNA–hybrid formation are important determinants of both telomere-length dynamics and proliferative potential after the inactivation of telomerase.Abstract:
Although telomeres are heterochromatic, they are transcribed into noncoding telomeric repeat-containing RNA (TERRA). Here we show that RNA-DNA hybrids form at telomeres and are removed by RNase H enzymes in the budding yeast, Saccharomyces cerevisiae. In recombination-competent telomerase mutants, telomeric RNA-DNA hybrids promote recombination-mediated elongation events that delay the onset of cellular senescence. Reduction of TERRA and telomeric RNA-DNA-hybrid levels diminishes rates of recombination-mediated telomere elongation in cis. Overexpression of RNase H decreases telomere recombination rates and accelerates senescence in recombination-competent but not recombination-deficient cells. In contrast, in the absence of both telomerase and homologous recombination, accumulation of telomeric RNA-DNA hybrids leads to telomere loss and accelerated rates of cellular senescence. Therefore, the regulation of TERRA transcription and telomeric RNA-DNA-hybrid formation are important determinants of both telomere-length dynamics and proliferative potential after the inactivation of telomerase.read more
Citations
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Journal ArticleDOI
Mechanisms of genome instability induced by RNA-processing defects.
TL;DR: How RNA-processing defects could destabilize genomes through mutagenic R-loop structures and by altering expression of genes required for genome stability are discussed.
Journal ArticleDOI
SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability
Eleonora Petti,Valentina Buemi,Antonina Zappone,Odessa Schillaci,Pamela Veneziano Broccia,Roberto Dinami,Silvia Matteoni,Roberta Benetti,Stefan Schoeftner +8 more
TL;DR: The authors identify the RNA interacting factors NONO and SFPQ as proteins that interact with TERRA and telomere chromatin and reveal putative roles for these factors in telomeres integry maintenance by interfering with RNA:DNA hybrid formation.
Journal ArticleDOI
Telomeric RNAs are essential to maintain telomeres
TL;DR: 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.
Journal ArticleDOI
Nuclear Noncoding RNAs and Genome Stability.
TL;DR: How ncRNAs inhibit spurious recombination among repetitive DNA elements, repress mobilization of transposable elements, template or bridge DNA double-strand breaks during repair, and direct developmentally regulated genome rearrangements in some ciliates are discussed.
Journal ArticleDOI
Telomeric repeat-containing RNA (TERRA) constitutes a nucleoprotein component of extracellular inflammatory exosomes.
Zhuo Wang,Zhuo Wang,Zhong Deng,Nadia Dahmane,Kevin Tsai,Pu Wang,Dewight Williams,Andrew V. Kossenkov,Louise C. Showe,Rugang Zhang,Qihong Huang,Jose R. Conejo-Garcia,Paul M. Lieberman +12 more
TL;DR: It is shown that noncoding telomere RNA transcripts [telomeric repeat-containing RNA (TERRA)] are secreted into the extracellular environment in exosome vesicle fractions, suggesting a previously unidentified extrinsic function for TERRA and a mechanism of communication between telomeres and innate immune signals in tissue and tumor microenvironments.
References
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Journal ArticleDOI
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
TL;DR: It is proposed that the novel telomere terminal transferase is involved in the addition of telomeric repeats necessary for the replication of chromosome ends in eukaryotes.
Journal ArticleDOI
Mammalian Telomeres End in a Large Duplex Loop
Jack D. Griffith,Laurey Comeau,Soraya Rosenfield,Rachel M. Stansel,Alessandro Bianchi,Heidi Moss,Titia de Lange +6 more
TL;DR: Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro, which may provide a general mechanism for the protection and replication of telomeres.
Journal ArticleDOI
Origin of concatemeric T7 DNA.
TL;DR: The observed concatemers of T7 DNA are consistent with replication schemes resulting in double-helical molecules with 3´ ended tails as discussed by the authors, and they can then join to form dimers which on further replication similarly form larger concatures.
Journal ArticleDOI
Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends.
TL;DR: It is demonstrated that mammalian telomeres are transcribed into telomeric repeat–containing RNA (TERRA), and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.
Journal ArticleDOI
An alternative pathway for yeast telomere maintenance rescues est1− senescence
TL;DR: It is shown that a minor subpopulation of est1- survivors arise as a result of the amplification and acquisition of subtelomeric elements (and their deletion derivatives) by a large number of telomeres, indicating that even when the primary pathway for telomere replication is defective, an alternative backup pathway can restore telomerre function and keep the cell alive.