A Novel NAD-RNA Decapping Pathway Discovered by Synthetic Light-Up NAD-RNAs

Abele, Florian; Höfer, Katharina; Bernhard, Patrick; Grawenhoff, Julia; Seidel, Maximilian; Krause, André; Kopf, Sara; Schröter, Martin; Jäschke, Andres

doi:10.3390/biom10040513

Cited by 14 publications

(22 citation statements)

References 57 publications

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“…When the activities of NAD + -dependent enzymes, such as CD38/157 and poly (ADP-ribose) polymerase-1 (PARP-1) are chronically increased, specifically under chronic inflammation and oxidative stress, this may lead to NAD + decline and a reduced substrate availability for sirtuins that are involved in antiaging signaling [8]. Supplementation with small molecular compounds used for NAD + biosynthesis, so-called NAD + precursors, such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nicotinamide (NA), has been found to exert preventive and therapeutic effects that ameliorated aging-associated pathophysiologies in animal models [10][11][12][13]. These emerging findings have brought a promising intervention, a socalled "NAD + boosting" strategy.…”

Section: Introductionmentioning

confidence: 99%

Cross-Sectional Associations between Dietary Daily Nicotinamide Intake and Patient-Reported Outcomes in Colorectal Cancer Survivors, 2 to 10 Years Post-Diagnosis

Bours

Koole

et al. 2021

Nutrients

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Supplementation with nicotinamide adenine dinucleotide (NAD+) precursors including dietary nicotinamide has been found to boost tissue NAD+ levels and ameliorate oxidative stress-induced damage that contributes to aging and aging-related diseases. The association between dietary NAD+ precursors and patient-reported health-related outcomes in cancer survivors has not been investigated. This study aimed to determine associations of dietary nicotinamide intake with different patient-reported outcomes in colorectal cancer survivors, 2 to 10 years post-diagnosis. A total of 145 eligible participants were recruited into this cross-sectional study. Dietary nicotinamide intake level was calculated based on data from 7-day food diaries. Fatigue was assessed with the Checklist Individual Strength (CIS), which is a subscale of the cancer-specific European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC), and anxiety and depression were assessed with Hospital Anxiety and Depression Scale (HADS). Oxidative stress marker serum protein carbonyl contents and serum NAD+ levels were measured. A hierarchical linear regression model with confounder adjustment was performed to analyze the association of nicotinamide intake, serum protein carbonyl contents, and NAD+ levels with patient-reported outcomes. The median values of daily nicotinamide intake for male and female participants were 19.1 and 14.4 mg, respectively. Daily dietary nicotinamide intake was associated with a lower level of fatigue (β: −14.85 (−28.14, −1.56)) and a lower level of anxiety and depression (β: −4.69 (−8.55, −0.83)). Subgroup analyses by sex showed that a beneficial association between nicotinamide intake and patient-reported outcomes was mainly found in men. To conclude, our findings suggested that higher dietary NAD+ precursor nicotinamide intake was cross-sectionally associated with less patient-reported outcomes in CRC survivors.

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Section: Introductionmentioning

confidence: 99%

Cross-Sectional Associations between Dietary Daily Nicotinamide Intake and Patient-Reported Outcomes in Colorectal Cancer Survivors, 2 to 10 Years Post-Diagnosis

Bours

Koole

et al. 2021

Nutrients

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“…In the CD38 knockout mouse, NADase activity was absent in all compartments, from plasma membranes to nuclei [ 193 ]. CD38 was shown to process NAD + -capped RNA in vitro into ADP-ribose-modified-RNA and nicotinamide [ 194 ]. CD38 degrades NAD + and also NMN and NADP, generating second messengers such as ADP ribose (ADPR), cADPR, and nicotinic acid adenine dinucleotide phosphate (NAADP).…”

Section: Mono(adp-ribosyl) Transferases (Mart)mentioning

confidence: 99%

Mono(ADP-ribosyl)ation Enzymes and NAD+ Metabolism: A Focus on Diseases and Therapeutic Perspectives

Poltronieri

Celetti

Palazzo

2021

Cells

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Mono(ADP-ribose) transferases and mono(ADP-ribosyl)ating sirtuins use NAD+ to perform the mono(ADP-ribosyl)ation, a simple form of post-translational modification of proteins and, in some cases, of nucleic acids. The availability of NAD+ is a limiting step and an essential requisite for NAD+ consuming enzymes. The synthesis and degradation of NAD+, as well as the transport of its key intermediates among cell compartments, play a vital role in the maintenance of optimal NAD+ levels, which are essential for the regulation of NAD+-utilizing enzymes. In this review, we provide an overview of the current knowledge of NAD+ metabolism, highlighting the functional liaison with mono(ADP-ribosyl)ating enzymes, such as the well-known ARTD10 (also named PARP10), SIRT6, and SIRT7. To this aim, we discuss the link of these enzymes with NAD+ metabolism and chronic diseases, such as cancer, degenerative disorders and aging.

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“…As recently discovered, ADPR-RNA can be also produced by hydrolysis of N-glycosidic bond of NAD-RNA by eukaryotic glycohydrolase CD38 in vitro ( figure 5 d ) [ 68 ].…”

Section: Adp-ribose Is a Potential New Major Non-canonical Rna 5′ Cap With At Least Four Possible Mechanisms For Cappingmentioning

confidence: 99%

The expanding field of non-canonical RNA capping: new enzymes and mechanisms

2021

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Recent years witnessed the discovery of ubiquitous and diverse 5′-end RNA cap-like modifications in prokaryotes as well as in eukaryotes. These non-canonical caps include metabolic cofactors, such as NAD + /NADH, FAD, cell wall precursors UDP-GlcNAc, alarmones, e.g. dinucleotides polyphosphates, ADP-ribose and potentially other nucleoside derivatives. They are installed at the 5′ position of RNA via template-dependent incorporation of nucleotide analogues as an initiation substrate by RNA polymerases. However, the discovery of NAD-capped processed RNAs in human cells suggests the existence of alternative post-transcriptional NC capping pathways. In this review, we compiled growing evidence for a number of these other mechanisms which produce various non-canonically capped RNAs and a growing repertoire of capping small molecules. Enzymes shown to be involved are ADP-ribose polymerases, glycohydrolases and tRNA synthetases, and may potentially include RNA 3′-phosphate cyclases, tRNA guanylyl transferases, RNA ligases and ribozymes. An emerging rich variety of capping molecules and enzymes suggests an unrecognized level of complexity of RNA metabolism.

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A Novel NAD-RNA Decapping Pathway Discovered by Synthetic Light-Up NAD-RNAs

Cited by 14 publications

References 57 publications

Cross-Sectional Associations between Dietary Daily Nicotinamide Intake and Patient-Reported Outcomes in Colorectal Cancer Survivors, 2 to 10 Years Post-Diagnosis

Cross-Sectional Associations between Dietary Daily Nicotinamide Intake and Patient-Reported Outcomes in Colorectal Cancer Survivors, 2 to 10 Years Post-Diagnosis

Mono(ADP-ribosyl)ation Enzymes and NAD+ Metabolism: A Focus on Diseases and Therapeutic Perspectives

The expanding field of non-canonical RNA capping: new enzymes and mechanisms

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