Sprouts of RNA epigenetics

Zheng, Guoliang; Dahl, John Arne; Niu, Yamei; Fu, Ye; Klungland, Arne; Yang, Ying; He, Chuan

doi:10.4161/rna.24711

Cited by 86 publications

(59 citation statements)

References 34 publications

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“…7,8 The functions of these latter enzymes are associated with important physiological pathways including metabolism and fertility. 8–10 Moreover, polymorphic variations in the FTO gene have been linked to breast and endometrial cancer risk. 11–13 …”

Section: Introductionmentioning

confidence: 99%

Structure and Thermodynamics of N⁶-Methyladenosine in RNA: A Spring-Loaded Base Modification

et al. 2015

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N6-Methyladenosine (m6A) modification is hypothesized to control processes such as RNA degradation, localization, and splicing. However, the molecular mechanisms by which this occurs are unclear. Here, we measured structures of an RNA duplex containing m6A in the GGACU consensus, along with an unmodified RNA control, by 2D NMR. The data show that m6A–U pairing in the double-stranded context is accompanied by the methylamino group rotating from its energetically preferred syn geometry on the Watson–Crick face to the higher-energy anti conformation, positioning the methyl group in the major groove. Thermodynamic measurements of m6A in duplexes reveal that it is destabilizing by 0.5–1.7 kcal/mol. In contrast, we show that m6A in unpaired positions base stacks considerably more strongly than the unmodified base, adding substantial stabilization in single-stranded locations. Transcriptome-wide nuclease mapping of methylated RNA secondary structure from human cells reveals a structural transition at methylated adenosines, with a tendency to single-stranded structure adjacent to the modified base.

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Section: Introductionmentioning

confidence: 99%

Structure and Thermodynamics of N⁶-Methyladenosine in RNA: A Spring-Loaded Base Modification

et al. 2015

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“…115 RNA methylation/hydroxymethylation is another cofactor-dependent (SAM/α-KG) epigenetic process that has been directly linked to obesity; however, the sensitivity of these enzymes to changes in cell metabolism has not been studied. 116 Finally, chromatin modifiers underwent a nomenclature change in 2007 due to the realization that many of these enzymes modify and regulate the function of non-histone proteins. 117 Understanding how metabolism co-regulates the posttranslational modification of histones, 25 transcription factors, 118 multiprotein complexes, 119 and metabolic enzymes 120 will be an important step to defining the feedback and feed-forward loops that connect metabolism and gene expression in vivo .…”

Section: Discussionmentioning

confidence: 99%

Metabolic Mechanisms of Epigenetic Regulation

Meier

2013

ACS Chem. Biol.

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Chromatin modifications have been well-established to play a critical role in the regulation of genome function. Many of these modifications are introduced and removed by enzymes that utilize cofactors derived from primary metabolism. Recently, it has been shown that endogenous cofactors and metabolites can regulate the activity of chromatin-modifying enzymes, providing a direct link between the metabolic state of the cell and epigenetics. Here we review metabolic mechanisms of epigenetic regulation with an emphasis on their role in cancer. Focusing on three core mechanisms, we detail and draw parallels between metabolic and chemical strategies to modulate epigenetic signaling, and highlight opportunities for chemical biologists to help shape our knowledge of this emerging phenomenon. Continuing to integrate our understanding of metabolic and genomic regulatory mechanisms may help elucidate the role of nutrition in diseases such as cancer, while also providing a basis for new approaches to modulate epigenetic signaling for therapeutic benefit.

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“…The importance of RNA modifications in biological systems is underscored by recent discoveries of modified ribonucleosides in virtually all forms of RNA, both coding and non-coding (Carlile et al, 2014; He, 2010; Kirino & Mourelatos, 2007; Ohara et al, 2007; Zheng et al, 2013). This importance is underscored by the advent of RNA sequencing and bioinformatics, which has led to the discovery of new non-coding RNA (ncRNA) species and the implication of ncRNA in a variety of host-pathogen interactions, genetic disorders and adaptive responses to stress (Arnvig & Young, 2012; C.…”

Section: Methodsmentioning

confidence: 99%

A Platform for Discovery and Quantification of Modified Ribonucleosides in RNA

Cai

Chionh

Hia

et al. 2015

Methods in Enzymology

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Here we describe an analytical platform for systems-level quantitative analysis of modified ribonucleosides in any RNA species, with a focus on stress-induced reprogramming of tRNA as part of a system of translational control of cell stress response. The chapter emphasizes strategies and caveats for each of the seven steps of the platform workflow: 1) RNA isolation, 2) RNA purification, 3) RNA hydrolysis to individual ribonucleosides, 4) chromatographic resolution of ribonucleosides, 5) identification of the full set of modified ribonucleosides, 6) mass spectrometric quantification of ribonucleosides, 6) interrogation of ribonucleoside datasets, and 7) mapping the location of stress-sensitive modifications in individual tRNA molecules. We have focused on the critical determinants of analytical sensitivity, specificity, precision and accuracy in an effort to ensure the most biologically meaningful data on mechanisms of translational control of cell stress response. The methods described here should find wide use in virtually any analysis involving RNA modifications.

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Sprouts of RNA epigenetics

Cited by 86 publications

References 34 publications

Structure and Thermodynamics of N⁶-Methyladenosine in RNA: A Spring-Loaded Base Modification

Structure and Thermodynamics of N⁶-Methyladenosine in RNA: A Spring-Loaded Base Modification

Metabolic Mechanisms of Epigenetic Regulation

A Platform for Discovery and Quantification of Modified Ribonucleosides in RNA

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Sprouts of RNA epigenetics

Cited by 86 publications

References 34 publications

Structure and Thermodynamics of N6-Methyladenosine in RNA: A Spring-Loaded Base Modification

Structure and Thermodynamics of N6-Methyladenosine in RNA: A Spring-Loaded Base Modification

Metabolic Mechanisms of Epigenetic Regulation

A Platform for Discovery and Quantification of Modified Ribonucleosides in RNA

Contact Info

Product

Resources

About

Structure and Thermodynamics of N⁶-Methyladenosine in RNA: A Spring-Loaded Base Modification

Structure and Thermodynamics of N⁶-Methyladenosine in RNA: A Spring-Loaded Base Modification