To unwind the biological knots: The <scp>DNA</scp>/<scp>RNA</scp> G‐quadruplex resolvase <scp>RHAU</scp> (<scp>DHX36</scp>) in development and disease

Yang, Chensi; Yao, Jie; Yi, Huijuan; Huang, Xinyi; Zhao, Wukui; Yang, Zhongzhou

doi:10.1002/ame2.12251

Cited by 3 publications

(2 citation statements)

References 55 publications

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“…The selected lncRNAs primarily participate in cell growth, epithelial-to-mesenchymal transition and apoptosis ( Table 5 ). Notably, among the listed RBPs in Table 5 , DHX36 has been previously reported to actively resolve G4s [ 57 , 58 ]. The other RBPs that were identified in our search are yet to be reported in direct contact with RNA G4s.…”

Section: Discussionmentioning

confidence: 99%

In Silico Identification of Potential Quadruplex Forming Sequences in LncRNAs of Cervical Cancer

Singh

Desai

Shah

et al. 2023

IJMS

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Long non-coding RNAs (lncRNAs) have emerged as auxiliary regulators of gene expression influencing tumor microenvironment, metastasis and radio-resistance in cancer. The presence of lncRNA in extracellular fluids makes them promising diagnostic markers. LncRNAs deploy higher-order structures to facilitate a complex range of functions. Among such structures, G-quadruplexes (G4s) can be detected or targeted by small molecular probes to drive theranostic applications. The in vitro identification of G4 formation in lncRNAs can be a tedious and expensive proposition. Bioinformatics-driven strategies can provide comprehensive and economic alternatives in conjunction with suitable experimental validation. We propose a pipeline to identify G4-forming sequences, protein partners and biological functions associated with dysregulated lncRNAs in cervical cancer. We identified 17 lncRNA clusters which possess transcripts that can fold into a G4 structure. We confirmed in vitro G4 formation in the four biologically active isoforms of SNHG20, MEG3, CRNDE and LINP1 by Circular Dichroism spectroscopy and Thioflavin-T-assisted fluorescence spectroscopy and reverse-transcriptase stop assay. Gene expression data demonstrated that these four lncRNAs can be potential prognostic biomarkers of cervical cancer. Two approaches were employed for identifying G4 specific protein partners for these lncRNAs and FMR2 was a potential interacting partner for all four clusters. We report a detailed investigation of G4 formation in lncRNAs that are dysregulated in cervical cancer. LncRNAs MEG3, CRNDE, LINP1 and SNHG20 are shown to influence cervical cancer progression and we report G4 specific protein partners for these lncRNAs. The protein partners and G4s predicted in lncRNAs can be exploited for theranostic objectives.

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Section: Discussionmentioning

confidence: 99%

In Silico Identification of Potential Quadruplex Forming Sequences in LncRNAs of Cervical Cancer

Singh

Desai

Shah

et al. 2023

IJMS

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“…RHAU (RNA helicase associated with AU-rich element), also known as DHX36 or G4R1, possesses RNA-binding and resolvase activity to unwind the G-quadruplex (G4) structures [80]. It plays important roles during muscle development and regeneration [81]. The expression level of RHAU protein in the mouse cardiac mesoderm shows a gradual decrease after birth and becomes very low in the adult.…”

Section: Rhau In Postnatal Heart Function and Neonatal Cardiac Regene...mentioning

confidence: 99%

RNA-Binding Proteins as Critical Post-Transcriptional Regulators of Cardiac Regeneration

Shi

2023

IJMS

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Myocardial injury causes death to cardiomyocytes and leads to heart failure. The adult mammalian heart has very limited regenerative capacity. However, the heart from early postnatal mammals and from adult lower vertebrates can fully regenerate after apical resection or myocardial infarction. Thus, it is of particular interest to decipher the mechanism underlying cardiac regeneration that preserves heart structure and function. RNA-binding proteins, as key regulators of post-transcriptional gene expression to coordinate cell differentiation and maintain tissue homeostasis, display dynamic expression in fetal and adult hearts. Accumulating evidence has demonstrated their importance for the survival and proliferation of cardiomyocytes following neonatal and postnatal cardiac injury. Functional studies suggest that RNA-binding proteins relay damage-stimulated cell extrinsic or intrinsic signals to regulate heart regenerative capacity by reprogramming multiple molecular and cellular processes, such as global protein synthesis, metabolic changes, hypertrophic growth, and cellular plasticity. Since manipulating the activity of RNA-binding proteins can improve the formation of new cardiomyocytes and extend the window of the cardiac regenerative capacity in mammals, they are potential targets of therapeutic interventions for cardiovascular disease. This review discusses our evolving understanding of RNA-binding proteins in regulating cardiac repair and regeneration, with the aim to identify important open questions that merit further investigations.

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To unwind the biological knots: The DNA/RNA G‐quadruplex resolvase RHAU (DHX36) in development and disease

Yang

Yao

et al. 2022

Anim Models and Exp Med

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G4 sequences are short fragments of 4-interval triple guanine (G) with frequent and ubiquitous distribution in the genome and RNA transcripts (Figure 1A). The G4 sequences are usually folded into secondary "knot" structure (G4 structure) via Hoogsteen hydrogen bond to exert negative regulation on a variety of biological processes, including DNA replication and transcription, mRNA translation, and telomere maintenance (Figure 1B). There are helicases to relieve the G4 structure barrier, and the known dual DNA/RNA G4 helicases are RHAU, DDX21, and DHX9.The discovery of RHAU dates back to 2004 when Dr. Yoshikuni Nagamine's laboratory in the Friedrich Miescher Institute for Biomedical Research (a part of the Novartis Research Foundation) in Basel, Switzerland, identified a new AU-rich element (ARE)-binding protein that was associated with the ARE fragment of the urokinase plasminogen activator mRNA. 1 This new protein was named RNA helicase associated with AU-rich elements (RHAU) and was found to promote the degradation of ARE-containing mRNAs. 1 Protein sequence analysis of RHAU demonstrated the identical amino acid composition with the ATP-dependent DEAD/DEAH-box helicase 36 (DDX36 or DHX36). 2 One year later, it was found that RHAU possessed the DNA G4 resolving activity to bind and unwind DNA G4 structure, and was hence called G4 resolvase 1 (G4R1). 3 By then, 3 names had been given to this protein: RHAU, DHX36, and G4R1. Afterwards, the G4 resolvase activity of RHAU was extended to RNA molecule through in vitro biochemical analysis. 4 These early pioneering studies have uncovered the primary property of RHAU as DNA/ RNA G4 resolvase/helicase to unwind the G4 secondary structure and laid a solid foundation for elucidating the biological function of RHAU in mouse models. Later on, Dr. Nagamine's group generated the global Rhau knockout mice that were embryonic lethal at around embryonic day 7.5 (E7.5), indicating the essential role of RHAU in mouse development. 5 A following study of hematopoietic-specific Rhau deletion mice revealed

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To unwind the biological knots: The DNA/RNA G‐quadruplex resolvase RHAU (DHX36) in development and disease

Cited by 3 publications

References 55 publications

In Silico Identification of Potential Quadruplex Forming Sequences in LncRNAs of Cervical Cancer

In Silico Identification of Potential Quadruplex Forming Sequences in LncRNAs of Cervical Cancer

RNA-Binding Proteins as Critical Post-Transcriptional Regulators of Cardiac Regeneration

To unwind the biological knots: The DNA/RNA G‐quadruplex resolvase RHAU (DHX36) in development and disease

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