Mitochondrial RNA capping: highly efficient 5’-RNA capping with NAD<sup>+</sup> and NADH by yeast and human mitochondrial RNA polymerase

Bird, Jeremy G.; Basu, Urmimala; Kuster, David; Ramachandran, Aparna; Grudzien-Nogalska, Ewa; Kiledjian, Megerditch; Temiakov, Dmitry; Patel, Smita S.; Ebright, Richard H.; Nickels, Bryce E.

doi:10.1101/381160

Cited by 26 publications

(48 citation statements)

References 65 publications

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“…Our findings of the widespread presence of NAD-RNAs are consistent with findings from human cells (9) and, together with discoveries from bacteria and yeast (6,8), indicate that NAD + capping of RNA is an ancient and conserved RNA modification. Unlike the m 7 G cap, the NAD + cap can be directly incorporated into transcripts as the initiating nucleotide by bacterial RNAP, eukaryotic nuclear RNAP II, and mitochondrial RNAP (mtRNAP) (7,10,11,24). Intriguingly, transcripts from chloroplasts were not found to be NAD + capped in our NAD captur-eSeq.…”

Section: Discussionmentioning

confidence: 80%

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

Yuan

Zhao

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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As the most common RNA cap in eukaryotes, the 7-methylguanosine (m7G) cap impacts nearly all processes that a messenger RNA undergoes, such as splicing, polyadenylation, nuclear export, translation, and degradation. The metabolite and redox agent, nicotinamide adenine diphosphate (NAD+), can be used as an initiating nucleotide in RNA synthesis to result in NAD+-capped RNAs. Such RNAs have been identified in bacteria, yeast, and human cells, but it is not known whether they exist in plant transcriptomes. The functions of the NAD+ cap in RNA metabolism or translation are still poorly understood. Here, through NAD captureSeq, we show that NAD+-capped RNAs are widespread in Arabidopsis thaliana. NAD+-capped RNAs are predominantly messenger RNAs encoded by the nuclear and mitochondrial genomes, but not the chloroplast genome. NAD+-capped transcripts from the nuclear genome appear to be spliced and polyadenylated. Furthermore, although NAD+-capped transcripts constitute a small proportion of the total transcript pool from any gene, they are enriched in the polysomal fraction and associate with translating ribosomes. Our findings implicate the existence of as yet unknown mechanisms whereby the RNA NAD+ cap interfaces with RNA metabolic processes as well as translation initiation. More importantly, our findings suggest that cellular metabolic and/or redox states may influence, or be regulated by, mRNA NAD+ capping.

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Section: Discussionmentioning

confidence: 80%

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

Yuan

Zhao

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…This conclusion may not apply in yeast mitochondria, however, where several lines of evidence suggest that transcriptional incorporation of the coenzyme is, in fact, an evolved feature. First, the mitochondrial transcription machinery exhibits NAD-mediated RNA initiation efficiencies that are at least tenfold higher, compared to the nuclear RNAP II 32 . Second, individual mRNA species in this organelle were found to be highly 5′-NAD modified, comprising up to 60% of the respective transcript pools.…”

Section: Discussionmentioning

confidence: 99%

Extensive 5′-surveillance guards against non-canonical NAD-caps of nuclear mRNAs in yeast

et al. 2020

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The ubiquitous redox coenzyme nicotinamide adenine dinucleotide (NAD) acts as a non-canonical cap structure on prokaryotic and eukaryotic ribonucleic acids. Here we find that in budding yeast, NAD-RNAs are abundant (>1400 species), short (<170 nt), and mostly correspond to mRNA 5′-ends. The modification percentage of transcripts is low (<5%). NAD incorporation occurs mainly during transcription initiation by RNA polymerase II, which uses distinct promoters with a YAAG core motif for this purpose. Most NAD-RNAs are 3′-truncated. At least three decapping enzymes, Rai1, Dxo1, and Npy1, guard against NAD-RNA at different cellular locations, targeting overlapping transcript populations. NAD-mRNAs are not translatable in vitro. Our work indicates that in budding yeast, most of the NAD incorporation into RNA seems to be disadvantageous to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs.

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“…NAD is initially incorporated into several thousands of transcripts by transcription initiation by RNAP II in a largely statistical manner reflecting the competition of NAD with the canonical initiator ATP. As in prokaryotes (Bird et al, 2016;Frindert et al, 2018;Vvedenskaya et al, 2018), the promoter sequence determines the efficiency of NAD incorporation, which is for most yeast nuclear transcripts between 1 and 5%. We observe that a YAAG motif supports efficient NAD incorporation by RNAPII in vivo, with the G at position 3 being particularly important.…”

Section: Discussionmentioning

confidence: 99%

Extensive 5’-Surveillance Guards Against Non-Canonical NAD-Caps of Nuclear mRNAs in Yeast

Zhang

Kuster

Schmidt

et al. 2020

Preprint

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In BriefIn budding yeast, most of the NAD incorporation into RNA seems to be accidental and undesirable to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs. Highlights• Yeast cells have thousands of short NAD-RNAs related to the 5'-ends of mRNAs • RNA polymerase II prefers a YAAG promoter motif for NAD incorporation into RNA• NAD-RNA is strongly guarded against by Rai1, Dxo1, and Npy1 decapping enzymes at different subcellular sites • In vitro, NAD-mRNAs are rejected from translation SummaryThe ubiquitous redox coenzyme nicotinamide adenine dinucleotide (NAD) acts as a non-canonical cap structure on prokaryotic and eukaryotic ribonucleic acids. Here we find that in budding yeast, NAD-RNAs are abundant (>1400 species), short (<170 nt), and mostly correspond to mRNA 5'-ends. The modification percentage is low (<5%). NAD is incorporated during the initiation step by RNA polymerase II, which uses distinct promoters with a YAAG core motif for this purpose. Most NAD-RNAs are 3'-truncated. At least three decapping enzymes, Rai1, Dxo1, and Npy1, guard against NAD-RNA at different cellular locations, targeting overlapping transcript populations. NAD-mRNAs do not support translation in vitro. Our work indicates that in budding yeast, most of the NAD incorporation into RNA seems to be accidental and undesirable to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs.

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Mitochondrial RNA capping: highly efficient 5’-RNA capping with NAD⁺ and NADH by yeast and human mitochondrial RNA polymerase

Cited by 26 publications

References 65 publications

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

Extensive 5′-surveillance guards against non-canonical NAD-caps of nuclear mRNAs in yeast

Extensive 5’-Surveillance Guards Against Non-Canonical NAD-Caps of Nuclear mRNAs in Yeast

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Mitochondrial RNA capping: highly efficient 5’-RNA capping with NAD+ and NADH by yeast and human mitochondrial RNA polymerase

Cited by 26 publications

References 65 publications

NAD + -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

NAD + -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

Extensive 5′-surveillance guards against non-canonical NAD-caps of nuclear mRNAs in yeast

Extensive 5’-Surveillance Guards Against Non-Canonical NAD-Caps of Nuclear mRNAs in Yeast

Contact Info

Product

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About

Mitochondrial RNA capping: highly efficient 5’-RNA capping with NAD⁺ and NADH by yeast and human mitochondrial RNA polymerase

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated

NAD ⁺ -capped RNAs are widespread in the Arabidopsis transcriptome and can probably be translated