Structure and function of the bacterial decapping enzyme NudC

Höfer, Katharina; Li, Sisi; Abele, Florian; Frindert, Jens; Schlotthauer, Jasmin; Grawenhoff, Julia; Du, Jiamu; Patel, Dinshaw J.; Jäschke, Andres

doi:10.1038/nchembio.2132

Cited by 79 publications

(116 citation statements)

References 32 publications

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“…Recent studies indicate a broad swath of cellular roles for ADP‐ribose, including chromatin remodeling, membrane protein ion channel gating, and a host of processes dependent upon ADP‐ribosylation; this suggests that Nudix ADP‐ribose pyrophosphohydrolases may play roles in many physiological contexts. Other hydrolases are involved in eukaryotic and bacterial mRNA decapping by recognizing either the 5′‐7‐methylguanosine or the NAD mRNA cap, respectively, initiating the process of mRNA degradation . Diadenosine polyphosphates (Ap n As) are structurally related hydrolase substrates implicated in modulating an alarmone response upon pathogen infection or other cellular stress events .…”

Section: Introductionmentioning

confidence: 99%

The evolution of function within the Nudix homology clan

Srouji

Park

et al. 2017

Proteins

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The Nudix homology clan encompasses over 80,000 protein domains from all three domains of life, defined by homology to each other. Proteins with a domain from this clan fall into four general functional classes: pyrophosphohydrolases, isopentenyl diphosphate isomerases (IDIs), adenine/guanine mismatch-specific adenine glycosylases (A/G-specific adenine glycosylases), and non-enzymatic activities such as protein/protein interaction and transcriptional regulation. The largest group, pyrophosphohydrolases, encompasses more than 100 distinct hydrolase specificities. To understand the evolution of this vast number of activities, we assembled and analyzed experimental and structural data for 205 Nudix proteins collected from the literature. We corrected erroneous functions or provided more appropriate descriptions for 53 annotations described in the Gene Ontology Annotation database in this family, and propose 275 new experimentally-based annotations. We manually constructed a structure-guided sequence alignment of 78 Nudix proteins. Using the structural alignment as a seed, we then made an alignment of 347 “select” Nudix homology domains, curated from structurally determined, functionally characterized, or phylogenetically important Nudix domains. Based on our review of Nudix pyrophosphohydrolase structures and specificities, we further analyzed a loop region downstream of the Nudix hydrolase motif previously shown to contact the substrate molecule and possess known functional motifs. This loop region provides a potential structural basis for the functional radiation and evolution of substrate specificity within the hydrolase family. Finally, phylogenetic analyses of the 347 select protein domains and of the complete Nudix homology clan revealed general monophyly with regard to function and a few instances of probable homoplasy.

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Section: Introductionmentioning

confidence: 99%

The evolution of function within the Nudix homology clan

Srouji

Park

et al. 2017

Proteins

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“…10a) [84]. As a more sensitive alternative to 19 F NMR experiments, a fluorescent inhibitor screening assay for DcpS based on P-F bond cleavage in m 7 GMPF and the use of a fluoride-sensitive chemosensor for product quantitation has been developed (Fig. 10b) [97].…”

Section: Phosphate-modified Cap Analogs As Molecular Probes For Cap-dmentioning

confidence: 99%

“…2a) [84]. The compounds were tested as 19 F NMR probes for cap-related processes. m 7 GTPF was used as a binding probe for eIF4E in a 19 F NMR assay based on changes in the transverse relaxation rate upon binding by the protein [84].…”

Section: Phosphate-modified Cap Analogs As Molecular Probes For Cap-dmentioning

confidence: 99%

“…The compounds were tested as 19 F NMR probes for cap-related processes. m 7 GTPF was used as a binding probe for eIF4E in a 19 F NMR assay based on changes in the transverse relaxation rate upon binding by the protein [84]. All three compounds: m 7 GMPF, m 7 GDPF, and m 7 GTPF, were found useful for monitoring activity of DcpS as they were cleaved by the enzyme to m 7 GMP and a corresponding fluorine-containing leaving group: a fluoride anion, fluoromonophosphate, and fluorodiphosphate, respectively.…”

Section: Phosphate-modified Cap Analogs As Molecular Probes For Cap-dmentioning

confidence: 99%

“…1d) [18], and other moieties attached to the 5 0 end of RNA by an oligophosphate bridge. The structure, biosynthesis, function, and degradation of these so-called bacterial caps have currently come under intense investigation [19][20][21][22].…”

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confidence: 99%

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Applications of Phosphate Modification and Labeling to Study (m)RNA Caps

Warmiński

Sikorski

Kowalska

et al. 2017

Phosphate Labeling and Sensing in Chemical Biology

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The cap is a natural modification present at the 5 0 ends of eukaryotic messenger RNA (mRNA), which because of its unique structural features, mediates essential biological functions during the process of gene expression. The core structural feature of the mRNA cap is an N7-methylguanosine moiety linked by a 5 0 -5 0 triphosphate chain to the first transcribed nucleotide. Interestingly, other RNA 5 0 end modifications structurally and functionally resembling the m 7 G cap have been discovered in different RNA types and in different organisms. All these structures contain the 'inverted' 5 0 -5 0 oligophosphate bridge, which is necessary for interaction with specific proteins and also serves as a cleavage site for phosphohydrolases regulating RNA turnover. Therefore, cap analogs containing oligophosphate chain modifications or carrying spectroscopic labels attached to phosphate moieties serve as attractive molecular tools for studies on RNA metabolism and modification of natural RNA properties. Here, we review chemical, enzymatic, and chemoenzymatic approaches that enable preparation of modified cap structures and RNAs carrying such structures, with emphasis on phosphate-modified mRNA cap analogs and their potential applications.M. Warminski and P. J. Sikorski have contributed equally to this work.

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Shaping the Bacterial Epitranscriptome—5′‐Terminal and Internal RNA Modifications

2021

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All domains of life utilize a diverse set of modified ribonucleotides that can impact the sequence, structure, function, stability, and the fate of RNAs, as well as their interactions with other molecules. Today, more than 160 different RNA modifications are known that decorate the RNA at the 5′‐terminus or internal RNA positions. The boost of next‐generation sequencing technologies sets the foundation to identify and study the functional role of RNA modifications. The recent advances in the field of RNA modifications reveal a novel regulatory layer between RNA modifications and proteins, which is central to developing a novel concept called “epitranscriptomics.” The majority of RNA modifications studies focus on the eukaryotic epitranscriptome. In contrast, RNA modifications in prokaryotes are poorly characterized. This review outlines the current knowledge of the prokaryotic epitranscriptome focusing on mRNA modifications. Here, it is described that several internal and 5′‐terminal RNA modifications either present or likely present in prokaryotic mRNA. Thereby, the individual techniques to identify these epitranscriptomic modifications, their writers, readers and erasers, and their proposed functions are explored. Besides that, still unanswered questions in the field of prokaryotic epitranscriptomics are pointed out, and its future perspectives in the dawn of next‐generation sequencing technologies are outlined.

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Structure and function of the bacterial decapping enzyme NudC

Cited by 79 publications

References 32 publications

The evolution of function within the Nudix homology clan

The evolution of function within the Nudix homology clan

Applications of Phosphate Modification and Labeling to Study (m)RNA Caps

Shaping the Bacterial Epitranscriptome—5′‐Terminal and Internal RNA Modifications

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