Several years ago, we refuted the dogma that telomeres are transcriptionally silenced. We demonstrated that telomeres are transcribed into the long noncoding telomeric repeat containing RNA (TERRA) in mammals and yeast. In the meantime, work from several laboratories demonstrated that telomere transcription is a conserved feature in eukaryotes. Furthermore, we made the unexpected discovery that TERRA associates with telomere post transcription by strand invasion forming DNA/RNA hybrid structures which are known as R-loops. Currently, we are investigating the molecular mechanism of R-loop formation as well as the functions of TERRA for telomere maintenance.
| Publications related to this project |
| Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J. Science. 2007. doi: 10.1126/science.1147182. The Rat1p 5’ to 3’ exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae Luke B, Panza A, Redon S, Iglesias N, Li Z, Lingner J. Mol. Cell. 2008. doi: 10.1016/j.molcel.2008.10.019. The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase Redon S, Reichenbach P, Lingner J. Nucleic acids research. 2010. doi: 10.1093/nar/gkq296 Subtelomeric repetitive elements determine TERRA regulation by Rap1/Rif and Rap1/Sir complexes in yeast Iglesias N, Redon S, Pfeiffer V, Dees M, Lingner J, Luke B. EMBO reports. 2011. doi: 10.1038/embor.2011.73. TERRA Promotes Telomere Shortening through Exonuclease 1-Mediated Resection of Chromosome Ends Pfeiffer V, Lingner J. Plos Genetics. 2012. doi: 10.1371/journal.pgen.1002747. A three-state model for the regulation of telomerase by TERRA and hnRNPA1 Redon S, Zemp I, Lingner J. Nucleic acids research. 2013. doi: 10.1093/nar/gkt695. The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening *Pfeiffer V, *Crittin J, Grolimund L, Lingner J. Embo Journal. 2013. doi: 10.1038/emboj.2013.217. TERRA-Reinforced Association of LSD1 with MRE11 Promotes Processing of Uncapped Telomeres Porro A, Feuerhahn S, Lingner J. Cell reports. 2014. doi: 10.1016/j.celrep.2014.01.022. Functional characterization of the TERRA transcriptome at damaged telomeres Porro A, Feuerhahn S, Delafontaine J, Riethman H, Rougemont J, Lingner J. Nature Communications. 2014. doi: 10.1038/ncomms6379. Telomere functions grounding on TERRA firma Azzalin CM, Lingner J. Trends In Cell Biology. 2015. doi: 10.1016/j.tcb.2014.08.007. A practical qPCR approach to detect TERRA, the elusive telomeric repeat-containing RNA Feretzaki M, Lingner J. Methods. 2017. doi: 10.1016/j.ymeth.2016.08.004. Transformation-induced stress at telomeres is counteracted through changes in the telomeric proteome including SAMHD1 Majerska J, Feretzaki M, Glousker G, Lingner J. Life Science Alliance. 2018. doi: 10.26508/lsa.201800121. Expression and differential regulation of human TERRA at several chromosome ends *Feretzaki M, *Nunes PR, Lingner J. RNA. 2019. doi: 10.1261/rna.072322.119. RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops. Feretzaki M, Pospisilova M, Valador Fernandes R, Lunardi T, *Krejci L, *Lingner J. Nature. 2020. doi: 10.1038/s41586-020-2815-6. The makings of TERRA R-loops at chromosome ends. Fernandes RV, Feretzaki M, Lingner J. Cell Cycle. 2021. doi: 10.1080/15384101.2021.1962638. Challenging endings: How telomeres prevent fragility. Glousker G, Lingner J. Bioessays. 2021. doi: 10.1002/bies.202100157. Detection of TERRA R-Loops at Human Telomeres. Glousker G, Fernandes RV, Feretzaki M, Lingner J. Methods Mol Biol. 2022. doi: 10.1007/978-1-0716-2477-7_11. |