Cap-like structures in bacterial RNA and epitranscriptomic modification

Jäschke, Andres; Höfer, Katharina; Nübel, Gabriele; Frindert, Jens

doi:10.1016/j.mib.2015.12.009

Cited by 48 publications

(39 citation statements)

References 34 publications

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“…Recently, the ubiquitous redox cofactor nicotinamide adenine dinucleotide (NAD) has been found to be covalently linked to bacterial RNA 3 , and recent work from our laboratory discovered a subset of small regulatory RNAs (sRNAs) in the bacterium Escherichia coli to be specifically 5’-modified with NAD in a cap-like manner 4 . This finding provides a new and unexpected link between redox biology, metabolism, and RNA processing 5 , and represents the first description of a prokaryotic cap 6,7 . The NAD cap stabilizes the sRNAs in vitro against endonucleolytic processing by RNase E 8 , the major player of RNA decay in E. coli , and against 5’-end modification by RNA pyrophosphohydrolase RppH 9 , which converts 5’-triphosphate RNA into 5’-monophosphate RNA and thereby triggers endonucleolytic processing 4 .…”

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confidence: 67%

“…The current study reveals that for NudC, the cleavage of NAD-capped RNA is carried out more efficiently than known small-molecule substrates NAD + and NADH. Considering that E. coli has 13 Nudix enzymes, many of which with unclear function, it is conceivable that these might serve to process RNAs capped with other non-standard cap moieties, such as nucleotide sugars, dinucleoside polyphosphates, or other dinucleotide coenzymes 5 .…”

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confidence: 99%

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Structure and function of the bacterial decapping enzyme NudC

et al. 2016

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RNA capping and decapping are thought to be distinctive features of eukaryotes. Recently, the redox cofactor NAD was discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD decapping enzyme in vitro and in vivo. Here, crystal structures of Escherichia coli NudC in complex with substrate NAD and with cleavage product NMN reveal the catalytic residues lining the binding pocket and principles underlying molecular recognition of substrate and product. Biochemical mutation analysis identifies the conserved Nudix motif as the catalytic center of the enzyme, which needs to be homodimeric as the catalytic pocket is composed of amino acids from both monomers. NudC is single-strand specific and has a purine preference for the 5’-terminal nucleotide. The enzyme strongly prefers NAD-RNA over NAD and binds to a diverse set of cellular RNAs in an unspecific manner.

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confidence: 67%

Section: Discussionmentioning

confidence: 99%

Structure and function of the bacterial decapping enzyme NudC

et al. 2016

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“… The chemical nature of the 5′ end of RNA is a key determinant of RNA stability, processing, localization, translation efficiency 1,2 , and has been proposed to provide a layer of “epitranscriptomic” gene regulation 3 . Recently it has been shown that some bacterial RNA species carry a 5′-end structure reminiscent of the 5′ 7-methylguanylate “cap” in eukaryotic RNA.…”

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confidence: 99%

“…Recently it has been shown that some bacterial RNA species carry a 5′-end structure reminiscent of the 5′ 7-methylguanylate “cap” in eukaryotic RNA. In particular, RNA species containing a 5′-end nicotinamide adenine dinucleotide (NAD + ) or 3′-desphospho-coenzyme A (dpCoA) have been identified in both Gram-negative and Gram-positive bacteria 3–6 . It has been proposed that NAD + , reduced NAD + (NADH), and dpCoA caps are added to RNA after transcription initiation, in a manner analogous to the addition of 7-methylguanylate caps 6–8 .…”

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The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA

Bird

Zhang

Tian

et al. 2016

Nature

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The chemical nature of the 5′ end of RNA is a key determinant of RNA stability, processing, localization, translation efficiency1,2, and has been proposed to provide a layer of “epitranscriptomic” gene regulation3. Recently it has been shown that some bacterial RNA species carry a 5′-end structure reminiscent of the 5′ 7-methylguanylate “cap” in eukaryotic RNA. In particular, RNA species containing a 5′-end nicotinamide adenine dinucleotide (NAD+) or 3′-desphospho-coenzyme A (dpCoA) have been identified in both Gram-negative and Gram-positive bacteria3–6. It has been proposed that NAD+, reduced NAD+ (NADH), and dpCoA caps are added to RNA after transcription initiation, in a manner analogous to the addition of 7-methylguanylate caps6–8. Here, we show instead that NAD+, NADH, and dpCoA are incorporated into RNA during transcription initiation, by serving as non-canonical initiating nucleotides (NCINs) for de novo transcription initiation by cellular RNA polymerase (RNAP). We further show that both bacterial RNAP and eukaryotic RNAP II incorporate NCIN caps, that promoter DNA sequences at and upstream of the transcription start site determine the efficiency of NCIN capping, that NCIN capping occurs in vivo, and that NCIN capping has functional consequences. We report crystal structures of transcription initiation complexes containing NCIN-capped RNA products. Our results define the mechanism and structural basis of NCIN capping, and suggest that NCIN-mediated “ab initio capping” may occur in all organisms

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“…This is due to mainly two reasons. First, the chemical modiication of the 5ʹ end of RNA is critical for RNA processing, localization, stability, translational eiciency, and epitranscriptomic regulation of gene expression [66]. Second, NAD is both a co-substrate for enzymes, such as the sirtuins and poly(adenosine diphosphate-ribose) polymerases, and a critical electron-carrying coenzyme for enzymes that catalyze oxidation-reduction reactions.…”

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Epitranscriptomics for Biomedical Discovery

Xiong¹,

Heruth²,

Jiang³

et al. 2017

Applications of RNA-Seq and Omics Strategies - From Microorganisms to Human Health

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Epitranscriptomics is a newly burgeoning ield pertaining to the complete delineation and elucidation of chemical modiications of nucleotides found within all classes of RNA that do not involve a change in the ribonucleotide sequence. More than 140 diverse and distinct nucleotide modiications have been identiied in RNA, dwaring the number of nucleotide modiications found in DNA. The majority of epitranscriptomic modiications have been identiied in ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA). However, in total, the knowledge of the occurrence, and speciically the function, of RNA modiications remains scarce. Recently, the rapid advancement of next-generation sequencing and mass spectrometry technologies have allowed for the identiication and functional characterization of nucleotide modiications in both protein-coding and non-coding RNA on a global, transcriptome scale. In this chapter, we will introduce the concepts of nucleotide modiication, summarize transcriptome-wide RNA modiication mapping techniques, highlight recent studies exploring the functions of RNA modiications and their association to disease, and inally ofer insight into the future progression of epitranscriptomics.

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Cap-like structures in bacterial RNA and epitranscriptomic modification

Cited by 48 publications

References 34 publications

Structure and function of the bacterial decapping enzyme NudC

Structure and function of the bacterial decapping enzyme NudC

The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA

Epitranscriptomics for Biomedical Discovery

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