RNA Damage and Its Implications in Genome Stability

DNA repair, Journal Year: 2025, Volume and Issue: 147, P. 103821 - 103821

Published: March 1, 2025

Language: Английский

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Chemical Strategies to Modulate and Manipulate RNA Epigenetic Modifications

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

ConspectusRNA epigenetics has rapidly emerged as a key frontier in chemical biology, revealing that modifications to RNA bases and riboses can fine-tune essential cellular processes such gene expression, translation, metabolic homeostasis. Traditionally, researchers have relied on manipulating the "writers," "erasers," "readers" of modifications─i.e., protein cofactors─to alter study these marks. Those enzyme-centric strategies, including small molecule inhibitors CRISPR/Cas-based genetic perturbations, been highly effective are advancing clinical applications. However, purely approaches for installing, removing, or transforming without enzyme disturbance offered distinct advantages, temporal control, reversibility, bypassing compensatory biological feedback mechanisms often arise with enzymatic inhibition. Every chemist should be concerned about modifications, because they represent striking intersection molecular recognition, organic transformation, function. The ability direct reactivity at specific nucleosides illuminate how individual impact overall regulation. Further, since improper modification damage patterns implicated cancer, disorders, neurodegeneration, repair tools potential diagnostic therapeutic interventions. Beyond medicine, agriculture also stands benefit from control nucleoside-based plant hormones, possibly leading improved crop productivity resilience.In this Account, we outline several innovative strategies tailored different classes modifications. Flavin-based bioorthogonal chemistry enabled demethylation N6-methyladenosine (m6A) independent endogenous demethylases, while oxidative reactions convert 5-methylcytidine (m5C) into formyl derivatives labeling sequencing. Nitrogen-oxide photochemical routes provided access selective removal side chain N6-isopentenyladenosine (i6A), offering insights both cell biology hormone research. We showcase rationally designed molecules rewire complex pathways, facilitating correction vinyl-adduct lesions otherwise resistant repair. These methods bypass constraints dependence, affording precision (e.g., via light activation) site-selective RNA. By strategically engineering reactivity, uncovered new epitranscriptomic phenomena, situ generation non-native modification, offer fresh capabilities imaging targeted manipulation callus development. Together, discoveries signal paradigm shift: complement even surpass conventional enzyme-based investigating, editing, repairing ramifications broad. Chemists leverage reactivities dissect underpinnings diseases linked dysregulation engineer next-generation therapeutic, diagnostic, sequencing platforms. Plant biologists apply same hone agronomic traits, seed vigor stress resilience. Ultimately, deepened mechanistic refined reaction design increased biocompatibility, epigenome is poised become one mainstream across fields spanning chemistry, medicine─fostering deeper understanding RNA's role health disease opening avenues precise

Language: Английский

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RNA–DNA Differences: Mechanisms, Oxidative Stress, Transcriptional Fidelity, and Health Implications

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 544 - 544

Published: April 30, 2025

RNA–DNA differences (RDDs) challenge the traditional view of RNA as a faithful copy DNA, arising through editing, transcriptional errors, and oxidative damage. Reactive oxygen species (ROS) play central role, inducing lesions like 8-oxo-guanine that compromise transcription translation, leading to dysfunctional proteins. This review explores biochemical basis RDDs, their exacerbation under stress, dual roles in cellular adaptation disease. RDDs contribute genomic instability are implicated cancers, neurodegenerative disorders, autoimmune diseases, while also driving phenotypic diversity. Drawing on terrestrial spaceflight studies, we highlight intersection RDD formation, dysfunction, proposing innovative mitigation approaches. Advancements detection quantification, along with ROS management therapies, offer new avenues restore homeostasis promote resilience. By positioning hallmark entropy, this underscores limits biological adaptation. Furthermore, prevalence guanine-rich codons antioxidant genes increases susceptibility ROS-induced lesions, linking redox instability, constrained These insights have profound implications for understanding aging, disease progression, adaptive mechanisms both space environments.

Language: Английский

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RNA dynamics in oxidative stress: From obscurity to mechanistic understanding in health and disease

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(46)

Published: Nov. 4, 2024

Emotions coordinate our behavior and physiological states during survival-salient events pleasurable interactions. Even though we are often consciously aware of current emotional state, such as anger or happiness, the mechanisms giving ...Emotions felt in body, somatosensory feedback has been proposed to trigger conscious experiences. Here reveal maps bodily sensations associated with different emotions using a unique topographical self-report method. In ...

Language: Английский

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