Regulation of Telomere Length by G-Quadruplex Telomere DNA- and TERRA-Binding Protein TLS/FUS

Takahama, Kentaro; Takada, Asami; Tada, Shota; Shimizu, Mai; Sayama, Kazutoshi; Kurokawa, Riki; Oyoshi, Takanori

doi:10.1016/j.chembiol.2013.02.013

Cited by 154 publications

(195 citation statements)

References 46 publications

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“…Some of these hybrid-binding proteins, such as nucleolin (Gonzá-lez et al 2009;Haeusler et al 2014) and FUS (Takahama et al 2013), were found in other studies to bind G-quadruplexes, which also are in non-B DNA conformations. However, not all proteins that bind G-quadruplexes bind RNA/DNA hybrids.…”

Section: Resultsmentioning

confidence: 99%

Human proteins that interact with RNA/DNA hybrids

et al. 2018

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RNA/DNA hybrids form when RNA hybridizes with its template DNA generating a three-stranded structure known as the R-loop. Knowledge of how they form and resolve, as well as their functional roles, is limited. Here, by pull-down assays followed by mass spectrometry, we identified 803 proteins that bind to RNA/DNA hybrids. Because these proteins were identified using in vitro assays, we confirmed that they bind to R-loops in vivo. They include proteins that are involved in a variety of functions, including most steps of RNA processing. The proteins are enriched for K homology (KH) and helicase domains. Among them, more than 300 proteins preferred binding to hybrids than double-stranded DNA. These proteins serve as starting points for mechanistic studies to elucidate what RNA/DNA hybrids regulate and how they are regulated.

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Section: Resultsmentioning

confidence: 99%

Human proteins that interact with RNA/DNA hybrids

et al. 2018

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“…TERRA can interact with telomeric DNA to form hybrid DNA-RNA G-quadruplexes, interact with components of the shelterin complex, and bind telomerase [58]. TERRA is also thought to play a role in organising and expanding telomeric heterochromatin [69] and to help in telomere homeostasis. Indeed, TERRA appears to be expressed at a higher rate from short telomeres, to nucleate enzyme clusters by binding to multiple telomerase copies, and to recruit them to its telomere of origin [67].…”

Section: Magnesium and Telomeresmentioning

confidence: 99%

Telomere Homeostasis: Interplay with Magnesium

Maguire

Neytchev

Talwar

et al. 2018

IJMS

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Telomere biology, a key component of the hallmarks of ageing, offers insight into dysregulation of normative ageing processes that accompany age-related diseases such as cancer. Telomere homeostasis is tightly linked to cellular metabolism, and in particular with mitochondrial physiology, which is also diminished during cellular senescence and normative physiological ageing. Inherent in the biochemistry of these processes is the role of magnesium, one of the main cellular ions and an essential cofactor in all reactions that use ATP. Magnesium plays an important role in many of the processes involved in regulating telomere structure, integrity and function. This review explores the mechanisms that maintain telomere structure and function, their influence on circadian rhythms and their impact on health and age-related disease. The pervasive role of magnesium in telomere homeostasis is also highlighted.

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“…Due to structural similarities between DNA and RNA G-quadruplexes, their binding proteins overlap significantly. Among the G-quadruplex-binding proteins are nucleolin, hnRNP, serin/arginine-rich splicing factor (SRSF) 1 and 9, splicing factor U2AF, ribosomal proteins [69], as well as TLS [51], TRF2 [53], FRM2 [65,66], and the RNA helicase associated with AU-rich element (RHAU) proteins [70]. Telomeres have been considered to be transcriptionally silent, but recently it was demonstrated that telomeres are transcribed into telomeric repeat-containing RNA (TERRA) [125].…”

Section: Proteins Involved In Interactions With Quadruplex Dnamentioning

confidence: 99%

DNA and RNA Quadruplex-Binding Proteins

Brázda

Hároníková

Liao

et al. 2014

IJMS

225

195

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Four-stranded DNA structures were structurally characterized in vitro by NMR, X-ray and Circular Dichroism spectroscopy in detail. Among the different types of quadruplexes (i-Motifs, minor groove quadruplexes, G-quadruplexes, etc.), the best described are G-quadruplexes which are featured by Hoogsteen base-paring. Sequences with the potential to form quadruplexes are widely present in genome of all organisms. They are found often in repetitive sequences such as telomeric ones, and also in promoter regions and 5' non-coding sequences. Recently, many proteins with binding affinity to G-quadruplexes have been identified. One of the initially portrayed G-rich regions, the human telomeric sequence (TTAGGG)n, is recognized by many proteins which can modulate telomerase activity. Sequences with the potential to form G-quadruplexes are often located in promoter regions of various oncogenes. The NHE III1 region of the c-MYC promoter has been shown to interact with nucleolin protein as well as other G-quadruplex-binding proteins. A number of G-rich sequences are also present in promoter region of estrogen receptor alpha. In addition to DNA quadruplexes, RNA quadruplexes, which are critical in translational regulation, have also been predicted and observed. For example, the RNA quadruplex formation in telomere-repeat-containing RNA is involved in interaction with TRF2 (telomere repeat binding factor 2) and plays key role in telomere regulation. All these fundamental examples suggest the importance of quadruplex structures in cell processes and their understanding may provide better insight into aging and disease development.

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Regulation of Telomere Length by G-Quadruplex Telomere DNA- and TERRA-Binding Protein TLS/FUS

Cited by 154 publications

References 46 publications

Human proteins that interact with RNA/DNA hybrids

Human proteins that interact with RNA/DNA hybrids

Telomere Homeostasis: Interplay with Magnesium

DNA and RNA Quadruplex-Binding Proteins

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