Telomeric repeat-containing RNA structure in living cells

Xu, Yan; Suzuki, Yuta; Ito, Kenichiro; Komiyama, Makoto

doi:10.1073/pnas.1001177107

Cited by 165 publications

(147 citation statements)

References 53 publications

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“…TERRA is an integral component of telomeric heterochromatin, forms distinct G-quadruplex structures in vitro and in vivo, and has been demonstrated to interact with critical epigenetic regulators that include LSD1 demethylase and SUV39H1 methyltransferase enzymes (Luke et al 2008;Schoeftner and Blasco 2008;Deng et al 2009;Xu et al 2010;Iglesias et al 2011;Lopez de Silanes et al 2014;Porro et al 2014a,b;Azzalin and Lingner 2015). Despite a correlation between histone H3K4/K9 methylation patterns and gene silencing at telomeres (Krogan et al 2002;Vaquero-Sedas et al 2012;Porro et al 2014b), it is unclear how these enzymes are recruited to telomeres and how they might function to mediate telomere structure and composition.…”

Section: Discussionmentioning

confidence: 99%

“…Although GQ RNA shape-based recognition is not well established, it is known that other protein domains can also preferentially recognize GQ-forming RNAs including: the arginine-glycine-glycine repeat (RGG) domain of Fragile-X mental retardation protein (FMRP), the glycine-argininerich (GAR) domain of TRF2, and the N-terminal domain of the DEAH-box ATP-dependent helicase 36 (DHX36) (Deng et al 2009;Meier et al 2013;Chen et al 2015;Vasilyev et al 2015). With the development of GQ-specific antibodies that have unambiguously identified GQ TERRA RNA structures in living cells (Xu et al 2010;Di Antonio et al 2012;Biffi et al 2013Biffi et al , 2014, more biophysical studies are needed that probe how protein domains and multidomain protein complexes recognize the molecular architecture of GQ RNAs. Our data have defined how TERRA's secondary and tertiary structural motifs can serve as recognition elements for LSD1 interactions by coupling biophysical studies (CD/AUC), EMSA, enzyme kinetics, XL-MS, and X-ray crystallographic methods.…”

Section: Discussionmentioning

confidence: 99%

“…A single GQ RNA unit and a stacked GQ RNA were prepared to investigate binding affinity and specificity of the GQ RNA-LSD1 interaction. The UUAGGG repeat elements of TERRA can form a stable parallel-stranded GQ RNA in vivo (Xu et al 2010) and a model of the higher order TERRA RNA architecture has been previously demonstrated (Martadinata and Phan 2013). Martadinata and Phan 2013;Balaratnam and Basu 2015).…”

Section: Monovalent Ions Dramatically Influence Terra Topologymentioning

confidence: 99%

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G-quadruplex RNA binding and recognition by the lysine-specific histone demethylase-1 enzyme

Hirschi

Martin

Luka

et al. 2016

RNA

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Lysine-specific histone demethylase 1 (LSD1) is an essential epigenetic regulator in metazoans and requires the co-repressor element-1 silencing transcription factor (CoREST) to efficiently catalyze the removal of mono-and dimethyl functional groups from histone 3 at lysine positions 4 and 9 (H3K4/9). LSD1 interacts with over 60 regulatory proteins and also associates with lncRNAs (TERRA, HOTAIR), suggesting a regulatory role for RNA in LSD1 function. We report that a stacked, intramolecular G-quadruplex (GQ) forming TERRA RNA (GG[UUAGGG] 8 UUA) binds tightly to the functional LSD1-CoREST complex (K d ≈ 96 nM), in contrast to a single GQ RNA unit ([UUAGGG] 4 U), a GQ DNA ([TTAGGG] 4 T), or an unstructured single-stranded RNA. Stabilization of a parallel-stranded GQ RNA structure by monovalent potassium ions (K + ) is required for high affinity binding to the LSD1-CoREST complex. These data indicate that LSD1 can distinguish between RNA and DNA as well as structured versus unstructured nucleotide motifs. Further, cross-linking mass spectrometry identified the primary location of GQ RNA binding within the SWIRM/amine oxidase domain (AOD) of LSD1. An ssRNA binding region adjacent to this GQ binding site was also identified via X-ray crystallography. This RNA binding interface is consistent with kinetic assays, demonstrating that a GQ-forming RNA can serve as a noncompetitive inhibitor of LSD1-catalyzed demethylation. The identification of a GQ RNA binding site coupled with kinetic data suggests that structured RNAs can function as regulatory molecules in LSD1-mediated mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Monovalent Ions Dramatically Influence Terra Topologymentioning

confidence: 99%

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G-quadruplex RNA binding and recognition by the lysine-specific histone demethylase-1 enzyme

Hirschi

Martin

Luka

et al. 2016

RNA

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“…These two have the same sequences ((UUAGGG) n vs. (TTAGGG) n ). Like telomere DNA, TERRA forms G-quadruplex either in vivo 370 or in vitro. 371 Some of the researchers claim that TERRA reveals a new level of regulation and protects chromosome ends, but others never agree with this idea.…”

Section: Determination Of Dna Nanostructures In Solutionsmentioning

confidence: 99%

Chemistry Can Make Strict and Fuzzy Controls for Bio-Systems: DNA Nanoarchitectonics and Cell-Macromolecular Nanoarchitectonics

Komiyama

Yoshimoto

Sisido

et al. 2017

Bulletin of the Chemical Society of Japan

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275

131

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In this review, we introduce two kinds of bio-related nanoarchitectonics, DNA nanoarchitectonics and cellmacromolecular nanoarchitectonics, both of which are basically controlled by chemical strategies. The former DNA-based approach would represent the precise nature of the nanoarchitectonics based on the strict or "digital" molecular recognition between nucleic bases. This part includes functionalization of single DNAs by chemical means, modification of the main-chain or side-chain bases to achieve stronger DNA binding, DNA aptamers and DNAzymes. It also includes programmable assemblies of DNAs (DNA Origami) and their applications for delivery of drugs to target sites in vivo, sensing in vivo, and selective labeling of biomaterials in cells and in animals. In contrast to the digital molecular recognition between nucleic bases, cell membrane assemblies and their interaction with macromolecules are achieved through rather generic and "analog" interactions such as hydrophobic effects and electrostatic forces. This cell-macromolecular nanoarchitectonics is discussed in the latter part of this review. This part includes bottom-up and top-down approaches for constructing highly organized cell-architectures with macromolecules, for regulating cell adhesion pattern and their functions in twodimension, for generating three-dimensional cell architectures on micro-patterned surfaces, and for building synthetic/natural macromolecular modified hybrid biointerfaces.

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“…22,23 Furthermore, G4DNA-containing regions can generate G4RNA-harbouring transcripts, which could further compromise downstream RNA-regulatory processes. 24 Although R-loops can provide an additional level of regulation of gene expression and possibly other chromosomal processes, aberrant R-loop accumulation is a major threat to genome stability. 17,25,26 Therefore, cells have evolved mechanisms to control R-loop levels across the genome (Fig.…”

mentioning

confidence: 99%