Oligonucleotide Models of Telomeric DNA and RNA Form a Hybrid G-quadruplex Structure as a Potential Component of Telomeres

Xu, Yan; Ishizuka, Takumi; Yang, Jie; Ito, Kenichiro; Katada, Hitoshi; Komiyama, Makoto; Hayashi, Tetsuya

doi:10.1074/jbc.m112.342030

Cited by 53 publications

(47 citation statements)

References 51 publications

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“…This is a general phenomenon rather than a situation associated to a specific sequence. Synthetic G-rich DNA and RNA oligomer forms HQ when they are mixed and incubated together (9,10), or delivered together into cells (35). With all the techniques available to us to identify the structure, our results show that HQ also forms in a dynamic physiological process.…”

Section: Resultsmentioning

confidence: 99%

Co-transcriptional formation of DNA:RNA hybrid G-quadruplex and potential function as constitutional cis element for transcription control

Zheng

Xiao

Liu

et al. 2013

Nucleic Acids Research

106

154

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G-quadruplex formation in genomic DNA is considered to regulate transcription. Previous investigations almost exclusively focused on intramolecular G-quadruplexes formed by DNA carrying four or more G-tracts, and structure formation has rarely been studied in physiologically relevant processes. Here, we report an almost entirely neglected, but actually much more prevalent form of G-quadruplexes, DNA:RNA hybrid G-quadruplexes (HQ) that forms in transcription. HQ formation requires as few as two G-tracts instead of four on a non-template DNA strand. Potential HQ sequences (PHQS) are present in >97% of human genes, with an average of 73 PHQSs per gene. HQ modulates transcription under both in vitro and in vivo conditions. Transcriptomal analysis of human tissues implies that maximal gene expression may be limited by the number of PHQS in genes. These features suggest that HQs may play fundamental roles in transcription regulation and other transcription-mediated processes.

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Section: Resultsmentioning

confidence: 99%

Co-transcriptional formation of DNA:RNA hybrid G-quadruplex and potential function as constitutional cis element for transcription control

Zheng

Xiao

Liu

et al. 2013

Nucleic Acids Research

106

154

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“…Evidence in support of this idea includes the observation that a fraction of TERRA remains associated with telomeric chromatin (Azzalin et al 2007;Schoeftner and Blasco 2008;Deng et al 2009) and dysfunction of the Rat1 ribonuclease leads to TERRA accumulation and telomere elongation defects in S. cerevisiae, both phenotypes being suppressed by RNase H overexpression (Luke et al 2008). Furthermore, both telomeric DNA and TERRA adopt G4-DNA structures (Phan 2010;Xu et al 2010;Lu et al 2013), and RNA-DNA hybrid G4 structures may represent a telomere component according to recent modeling studies (Xu et al 2012a). The existence of telomeric R-loops has been recently shown in budding yeast in two independent studies.…”

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confidence: 93%

Transcription and Recombination: When RNA Meets DNA

Aguilera

Gaillard

2014

Cold Spring Harbor Perspectives in Biology

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Correspondence: aguilo@us.es A particularly relevant phenomenon in cell physiology and proliferation is the fact that spontaneous mitotic recombination is strongly enhanced by transcription. The most accepted view is that transcription increases the occurrence of double-strand breaks and/or singlestranded DNA gaps that are repaired by recombination. Most breaks would arise as a consequence of the impact that transcription has on replication fork progression, provoking its stalling and/or breakage. Here, we discuss the mechanisms responsible for the cross talk between transcription and recombination, with emphasis on (1) the transcription -replication conflicts as the main source of recombinogenic DNA breaks, and (2) the formation of cotranscriptional R-loops as a major cause of such breaks. The new emerging questions and perspectives are discussed on the basis of the interference between transcription and replication, as well as the way RNA influences genome dynamics.H omologous recombination (HR) is a conserved pathway responsible for the repair of double-strand breaks (DSBs). In mitotic cells, DSBs may be induced by genotoxic agents, such as g irradiation or may occur spontaneously, in most of the cases in association with replication. Although HR represents one of the two main mechanisms of DSB repair, the other being nonhomologous end joining (NHEJ), eukaryotic cells favor HR as the preferential DSB repair pathway during the S/G 2 phases of the cell cycle, when the sister chromatid is available as template for error-free repair. Thus, HR events are regulated at different steps along the cell cycle, among others by the cyclin-dependent kinase 1 during 5 0 -end resection to guarantee its occurrence at S/G 2 (Heyer et al. 2010;Huertas 2010). Consequently, spontaneous mitotic recombination events are generally interpreted as the result of DSB repair during S/G 2 , although it cannot be disregarded that recombination could also be initiated by singlestranded DNA (ssDNA) gaps generated during replication.Spontaneous mitotic recombination might, in principle, take place anywhere in the genome with similar probability. However, as for mutations, both recombination and chromosome breakages occur more frequently in particular regions, referred to as hot spots. Those hot spots might arise from different local features, including the formation of non-B secondary structures, chromatin compaction, DNA-protein barriers to replication, or low-replication initi- . Nevertheless, the most extended and physiological relevant feature enhancing the probability of recombination is likely to be transcription (Aguilera 2002;Kim and Jinks-Robertson 2012;Gaillard et al. 2013). From bacteria to humans, a large body of evidence has accumulated showing that transcription stimulates spontaneous recombination, a phenomenon referred to as transcription-associated recombination (TAR). As replication failures seem to be the main source of recombinogenic DSBs, our actual view is that the major mechanism by which transcription stimulates recom...

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“…1,2 Human telomeric RNA performs various biofunctions, such as the regulation of the telomere length, 3–12 heterochromatin formation, 13,14 and end protection. 15,16 Recent studies suggest that telomeric RNA forms a G-quadruplex that plays an important role in telomere protection and regulation. 3,16,17 We and others have shown that human telomeric RNA forms G-quadruplex structures.…”

Section: Introductionmentioning

confidence: 99%

“…15,16 Recent studies suggest that telomeric RNA forms a G-quadruplex that plays an important role in telomere protection and regulation. 3,16,17 We and others have shown that human telomeric RNA forms G-quadruplex structures. 18–24 Additionally, we have demonstrated that telomeric RNA G-quadruplex structures play an important role in providing a protective structure to the telomere ends.…”

Section: Introductionmentioning

confidence: 99%

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Structure-Dependent Binding of hnRNPA1 to Telomere RNA

et al. 2017

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Telomeric repeat-containing RNA is a new noncoding RNA molecule that performs various biofunctions. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an RNA-binding protein involved in the telomere maintenance machinery. To date, little is known about how hnRNPA1 binds to telomeric RNA. In this study, we investigated the binding affinity and recognition mechanism of telomere RNA with the RNA recognition motif of hnRNPA1. Using the photochemical cross-linking method, we showed that the telomere RNA G-quadruplex with loops is important in the interaction of telomere RNA with hnRNPA1. Using small-molecule probes, we directly visualized the complex formed by the telomere RNA G-quadruplex and hnRNPA1 in vitro and in live cells. The results suggested that the structure-dependent binding of hnRNPA1 to telomere RNA regulates the telomere function. Therefore, our study provides new insights into the interactions between the RNA G-quadruplex and proteins at the telomere.

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Oligonucleotide Models of Telomeric DNA and RNA Form a Hybrid G-quadruplex Structure as a Potential Component of Telomeres

Cited by 53 publications

References 51 publications

Co-transcriptional formation of DNA:RNA hybrid G-quadruplex and potential function as constitutional cis element for transcription control

Co-transcriptional formation of DNA:RNA hybrid G-quadruplex and potential function as constitutional cis element for transcription control

Transcription and Recombination: When RNA Meets DNA

Structure-Dependent Binding of hnRNPA1 to Telomere RNA

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