FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2412824599> ?p ?o ?g. }

• W2412824599 endingPage "934" @default.
• W2412824599 startingPage "933" @default.
• W2412824599 abstract "News & Views3 June 2016free access TERRA Incognita at chromosome ends Stéphane Coulon Stéphane Coulon Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille Université, Institut Paoli-Calmettes, Marseille, France Equipe labellisée Ligue Search for more papers by this author Vincent Géli Vincent Géli [email protected] Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille Université, Institut Paoli-Calmettes, Marseille, France Equipe labellisée Ligue Search for more papers by this author Stéphane Coulon Stéphane Coulon Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille Université, Institut Paoli-Calmettes, Marseille, France Equipe labellisée Ligue Search for more papers by this author Vincent Géli Vincent Géli [email protected] Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille Université, Institut Paoli-Calmettes, Marseille, France Equipe labellisée Ligue Search for more papers by this author Author Information Stéphane Coulon1,2 and Vincent Géli1,2 1Marseille Cancer Research Center (CRCM), U1068 Inserm, UMR7258 CNRS, Aix Marseille Université, Institut Paoli-Calmettes, Marseille, France 2Equipe labellisée Ligue EMBO Reports (2016)17:933-934https://doi.org/10.15252/embr.201642583 See also: M Moravec et al (July 2016) PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Telomeres are transcribed in long noncoding RNA named TERRA. Although TERRA functions have been extensively investigated, the role of TERRA in telomerase recruitment and regulation is still elusive. In this issue of EMBO Reports, Moravec et al report in Schizosaccharomyces pombe that telomere shortening induces the expression of TERRA 1. They show that polyadenylated TERRA molecules specifically associate with the telomerase catalytic subunit and stimulate telomerase-mediated elongation of the telomere from which the TERRA molecules originate. Strikingly, their results indicate that shaping the 3′ end of telomere transcripts controls telomerase activity. Telomeres consist of DNA repeats associated with proteins, which constitutes a peculiar form of chromatin that protects the ends of chromosomes from degradation, fusion, and activation of DNA damage responses. Telomeres comprise arrays of G-rich tandem DNA repeats with a single-stranded extension on the 3′ strand called G-tail. Telomeric DNA is bound by the shelterin complex that bridges the duplex telomeric DNA to the G-tail. Various combinations of this canonical structure are found in different organisms. In contrast to yeast telomeres that adopt a non-nucleosomal chromatin structure, mammalian telomeric chromatin contains arrays of shelterin complexes flanked by nucleosomes. Despite these differences, telomeres and subtelomeric regions are heterochromatic in nature and create a transcriptionally repressive chromatin environment. In spite of this, telomeres were found to be transcribed by RNA polymerase II, which reads the C-rich telomeric strand to generate G-rich telomeric repeat-containing RNA, called TERRA 2. Transcription of TERRA starts within the adjacent subtelomeric sequences and includes a variable number of telomeric G-rich sequences. TERRA was initially discovered in mammalian cells and then in other eukaryotes including budding yeast, zebrafish, and plants 3. TERRA transcripts have been proposed to have several functions including telomeric heterochromatin formation, capping of chromosome ends, telomere replication, and regulation of telomerase activity; however, their precise molecular roles remain to be carefully elucidated. Moreover, conflicting data have been reported regarding the localization of TERRA and its role in telomerase recruitment and activity. For instance, in budding yeast accumulation of TERRA induced by the inactivation of the Rat1 5′ to 3′ exonuclease affected telomerase-mediated telomere elongation 4, while in another study TERRA molecules were proposed to participate in telomerase-dependent elongation of the transcribed telomere by aggregating telomerase molecules at short telomeres 56. Similarly, human TERRA was shown in vitro to be a natural ligand and direct inhibitor of human telomerase 78; however, overexpression of TERRA in cells lacking the two DNA methyltransferases DNMT1 and DNMT3b did not affect telomerase activity 9. These examples point out the need for unifying models integrating all these observations. …shaping the 3′ ends of TERRA transcripts by transcription termination may control telomerase activity In this issue of EMBO Reports, Moravec et al assess the role of TERRA in the regulation of telomerase activity in the fission yeast Schizosaccharomyces pombe. As with budding yeast and mammals, S. pombe contains G-rich TERRA molecules and subtelomeric RNA species transcribed in the opposite direction of TERRA (ARRET) 10. In the paper in this issue, the authors first show that telomere shortening induces the expression of TERRA in S. pombe as previously reported in budding yeast. However, in contrast to budding yeast only a subset of these TERRA molecules are polyadenylated. Strikingly, these polyadenylated TERRA molecules that are characterized by the presence of very short telomeric tracts at their 3′ end associate in RNA immunoprecipitation (RIP) experiments with telomerase in a way that is independent of telomerase RNA. Although there is no direct evidence that the catalytic subunit of telomerase binds TERRA directly, this raises the intriguing questions as to what the molecular basis of this interaction is and why telomerase or its associated proteins interact only with polyadenylated TERRA with short telomeric tracts. The authors further generate a transcriptionally inducible telomere (tiTEL) in order to force the transcription of one given telomere. With this experimental setting, induction of the expression of tiTEL produces higher amounts of polyadenylated tiTERRA than G-rich tiTERRA. The polyadenylated tiTERRA was found to associate with telomerase, and expression of tiTERRA leads to the specific elongation of the transcribed telomere in a telomerase-dependent manner without affecting the length of other telomeres. From these data, Moravec et al propose a model whereby shortening of telomeres and consecutive loss of Rap1 repression would increase TERRA transcription and release of polyadenylated TERRA into the nucleoplasm, where it would interact with telomerase and bring it back to its telomere of origin. In agreement with the model suggested by Cusanelli et al in budding yeast, interaction of telomerase with polyadenylated TERRA would promote telomerase recruitment and elongation of the telomere from which the TERRA molecules originate. Two main questions remain to be answered. First, is the interaction between polyadenylated TERRA and the catalytic subunit of telomerase direct? This question could be solved by the use of the CRAC method (cross-linking and analysis of cDNA) developed by Markus Bohnsack to identify potential interaction sites of telomerase with polyadenylated TERRA. The second question is how is polyadenylated TERRA with short telomeric tracts generated? Overall, the work by Moravec has three important merits: (i) It shows that polyadenylated TERRA interacts with telomerase, (ii) it provides evidence that telomere transcription stimulates telomerase-mediated telomere elongation in cis in an organism with human-like telomeres, and (iii) it proposes that different TERRA molecules may have opposing effects on telomerase activity. In Fig 1, we speculate how transcription termination could shape the 3′ ends of TERRA transcripts and lead to different TERRA molecules with opposing effects. TERRA molecules processed by the cleavage and polyadenylation factor (CPF)–cleavage factor (CF) complex would generate polyadenylated TERRA with no (or very short) telomeric sequences. These polyadenylated TERRA molecules would promote telomerase activity by nucleating telomerase at chromosome ends. Other pathways involved in TERRA termination—that remain to be determined—could generate TERRA with long telomeric tracts that would exert an inhibitory effect on telomerase. This hypothesis could reconcile some of the apparently conflicting results described above. After many efforts to understand how TERRA transcription is initiated, this work from Azzalin and co-workers points out the need to determine the mechanisms underlying TERRA transcription termination. Indeed, shaping the 3′ ends of TERRA transcripts by transcription termination may control telomerase activity. Figure 1. Processing of the 3′ end of telomere transcripts controls telomerase activityIn response to telomere erosion, Rap1 is released from telomeres, and G-rich TERRA transcription is induced. G-rich TERRA molecules exert an inhibitory effect on telomerase by competing with telomeres for telomerase binding. Moravec et al show that G-rich TERRA molecules are cleaved and polyadenylated, presumably by CPF-CF, thereby generating polyadenylated TERRA molecules containing few or no telomeric sequences. In this scenario, the G-rich TERRA would be degraded by the 5′–3′ exoribonuclease Dhp1/Rat1/Xrn2. The polyadenylated TERRA generated by the termination pathway interacts with the catalytic subunit of telomerase and promotes the nucleation of telomerase at the transcribed telomere. As a result, the short telomere is specifically elongated. In this model, we expect mutations affecting the exoribonuclease activity to inhibit telomerase activity. Download figure Download PowerPoint References Moravec M, Wischnewski H, Bah A et al (2016) EMBO Rep 17: 999–1012Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Azzalin CM, Reichenbach P, Khoriauli L et al (2007) Science 318: 798–801CrossrefCASPubMedWeb of Science®Google Scholar Azzalin CM, Lingner J (2014) Trends Cell Biol 25: 29–36CrossrefCASPubMedWeb of Science®Google Scholar Luke B, Panza A, Redon S et al (2008) Mol Cell 32: 465–477CrossrefCASPubMedWeb of Science®Google Scholar Gallardo F, Laterreur N, Cusanelli E et al (2011) Mol Cell 44: 819–827CrossrefCASPubMedWeb of Science®Google Scholar Cusanelli E, Romero CAP, Chartrand P (2013) Mol Cell 51: 780–791CrossrefCASPubMedWeb of Science®Google Scholar Schoeftner S, Blasco MA (2007) Nature 10: 228–236Web of Science®Google Scholar Redon S, Reichenbach P, Lingner J (2010) Nucleic Acids Res 38: 5797–5806CrossrefCASPubMedWeb of Science®Google Scholar Farnung BO, Brun CM, Arora R et al (2012) PLoS One 7: e35714CrossrefCASPubMedWeb of Science®Google Scholar Bah A, Wischnewski H, Shchepachev V et al (2012) Nucleic Acids Res 40: 2995–3005CrossrefCASPubMedWeb of Science®Google Scholar Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 17,Issue 7,July 2016Cover: Immunohistochemistry images of RAB2A of human breast cancer tissues are overlapped with invasive breast cancer spheroids to depict the ability of the protein to promote a cancer invasive program through regulation of MT1‐MMP post‐endocytic (top right) and E‐cadherin Golgi‐to‐PM (bottom left) trafficking. From Hiroaki Kajiho, Giorgio Scita and colleagues: RAB2A controls MT1‐MMP endocytic and E‐cadherin polarized Golgi trafficking to promote invasive breast cancer programs. For detail, see Article on page 1061. Scientific images by Hiroaki Kajiho, IFOM Foundation, Institute FIRC of Molecular Oncology. Cover art by Hiroaki Kajiho and Emanuela Frittoli, IFOM Foundation, Institute FIRC of Molecular Oncology. Volume 17Issue 71 July 2016In this issue FiguresReferencesRelatedDetailsLoading ..." @default.
• W2412824599 created "2016-06-24" @default.
• W2412824599 creator A5034247890 @default.
• W2412824599 creator A5076917810 @default.
• W2412824599 date "2016-06-03" @default.
• W2412824599 modified "2023-10-09" @default.
• W2412824599 title "TERRA Incognita at chromosome ends" @default.
• W2412824599 cites W1985214157 @default.
• W2412824599 cites W2001677411 @default.
• W2412824599 cites W2024406051 @default.
• W2412824599 cites W2049376070 @default.
• W2412824599 cites W2062779626 @default.
• W2412824599 cites W2073204556 @default.
• W2412824599 cites W2075029265 @default.
• W2412824599 cites W2137986693 @default.
• W2412824599 cites W2169532007 @default.
• W2412824599 cites W2346703054 @default.
• W2412824599 doi "https://doi.org/10.15252/embr.201642583" @default.
• W2412824599 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4931555" @default.
• W2412824599 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27259461" @default.
• W2412824599 hasPublicationYear "2016" @default.
• W2412824599 type Work @default.
• W2412824599 sameAs 2412824599 @default.
• W2412824599 citedByCount "2" @default.
• W2412824599 countsByYear W24128245992020 @default.
• W2412824599 crossrefType "journal-article" @default.
• W2412824599 hasAuthorship W2412824599A5034247890 @default.
• W2412824599 hasAuthorship W2412824599A5076917810 @default.
• W2412824599 hasBestOaLocation W24128245992 @default.
• W2412824599 hasConcept C104317684 @default.
• W2412824599 hasConcept C120804375 @default.
• W2412824599 hasConcept C151730666 @default.
• W2412824599 hasConcept C2778830712 @default.
• W2412824599 hasConcept C2780617777 @default.
• W2412824599 hasConcept C30481170 @default.
• W2412824599 hasConcept C54355233 @default.
• W2412824599 hasConcept C78458016 @default.
• W2412824599 hasConcept C86803240 @default.
• W2412824599 hasConceptScore W2412824599C104317684 @default.
• W2412824599 hasConceptScore W2412824599C120804375 @default.
• W2412824599 hasConceptScore W2412824599C151730666 @default.
• W2412824599 hasConceptScore W2412824599C2778830712 @default.
• W2412824599 hasConceptScore W2412824599C2780617777 @default.
• W2412824599 hasConceptScore W2412824599C30481170 @default.
• W2412824599 hasConceptScore W2412824599C54355233 @default.
• W2412824599 hasConceptScore W2412824599C78458016 @default.
• W2412824599 hasConceptScore W2412824599C86803240 @default.
• W2412824599 hasIssue "7" @default.
• W2412824599 hasLocation W24128245991 @default.
• W2412824599 hasLocation W24128245992 @default.
• W2412824599 hasLocation W24128245993 @default.
• W2412824599 hasLocation W24128245994 @default.
• W2412824599 hasOpenAccess W2412824599 @default.
• W2412824599 hasPrimaryLocation W24128245991 @default.
• W2412824599 hasRelatedWork W1828691184 @default.
• W2412824599 hasRelatedWork W1991523530 @default.
• W2412824599 hasRelatedWork W2002128513 @default.
• W2412824599 hasRelatedWork W2010134021 @default.
• W2412824599 hasRelatedWork W2031436818 @default.
• W2412824599 hasRelatedWork W2087157005 @default.
• W2412824599 hasRelatedWork W2119103177 @default.
• W2412824599 hasRelatedWork W2901845554 @default.
• W2412824599 hasRelatedWork W4295759162 @default.
• W2412824599 hasRelatedWork W2092874662 @default.
• W2412824599 hasVolume "17" @default.
• W2412824599 isParatext "false" @default.
• W2412824599 isRetracted "false" @default.
• W2412824599 magId "2412824599" @default.
• W2412824599 workType "article" @default.