Pseudouridine: the fifth RNA nucleotide with renewed interests

Li, Xiaoyu; Ma, Shiqing; Yi, Chengqi

doi:10.1016/j.cbpa.2016.06.014

Cited by 123 publications

(94 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1) of microbial origin, are widely-distributed biological molecules in which the base and ribosyl moieties are linked via a structurally conserved C -glycosidic bond (1, 2). Pseudouridine, the first discovered C -nucleoside, is the most prevalent of the over one hundred different modified nucleosides found in eukaryotic RNA (3). Moreover, a pseudouridine metabolic pathway from E. coli has been previously reported and well-characterized (4).…”

Section: Introductionmentioning

confidence: 99%

Comparative investigation into formycin A and pyrazofurin A biosynthesis reveals branch pathways for the construction ofC-nucleoside scaffolds

Zhang

et al. 2019

Preprint

View full text Add to dashboard Cite

24Formycin A (FOR-A) and pyrazofurin A (PRF-A) are purine-related C-nucleoside 25 antibiotics, in which ribose and a pyrazole-derived base are linked by a C-glycosidic 26 bond, however, the logic underlying the biosynthesis of these molecules has 27 remained largely unexplored. Here, we report the discovery of the pathways for 28 FOR-A and PRF-A biosynthesis from diverse actinobacteria, and demonstrate that 29 their biosynthesis is initiated by a lysine N 6 -monooxygenase. Moreover, we show 30 that the forT and prfE (individually related to FOR-A and PRF-A biosynthesis) 31 mutants are correspondingly capable of accumulating the unexpected 32 pyrazole-related intermediates, compound 11 and 9a. We also decipher the 33 enzymatic basis of ForT/PrfE for the C-glycosidic bond formation in FOR-A/PRF-A 34 biosynthesis. To our knowledge, ForT/PrfE represents the first example of β-RFA-P 35 (β-ribofuranosyl-aminobenzene 5'-phosphate) synthase-like enzymes governing 36 C-nucleoside scaffold construction in natural product biosynthesis. These data 37 establish a foundation for combinatorial biosynthesis of related purine nucleoside 38 antibiotics, and also open the way for target-directed genome mining of 39

show abstract

Section: Introductionmentioning

confidence: 99%

Comparative investigation into formycin A and pyrazofurin A biosynthesis reveals branch pathways for the construction ofC-nucleoside scaffolds

Zhang

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Genomewide mapping studies of the epitranscriptome in human cells have revealed widespread post‐transcriptional modifications in both non‐coding and coding RNA . Pseudouridine (ψ), the most common RNA modification, has been suggested to play a role in RNA stability, RNA folding/secondary structure, and translation efficiency and fidelity; however, the functional consequences of this modification at the cellular level, especially in mRNA, generally remain obscure . Human cells contain 13 pseudouridine synthases, but the majority remain uncharacterized, and their substrates and subcellular distribution are unknown .…”

Section: Introductionmentioning

confidence: 99%

“…Pseudouridine (ψ), the most common RNA modification, has been suggested to play a role in RNA stability, RNA folding/secondary structure, and translation efficiency and fidelity; however, the functional consequences of this modification at the cellular level, especially in mRNA, generally remain obscure . Human cells contain 13 pseudouridine synthases, but the majority remain uncharacterized, and their substrates and subcellular distribution are unknown . The mitochondrial 16S rRNA contains a single known pseudouridine site , and mitochondrial tRNAs are extensively pseudouridylated by PUS1, an enzyme that also modifies cytosolic tRNAs, and when mutated causes mitochondrial myopathy and sideroblastic anemia .…”

Section: Introductionmentioning

confidence: 99%

A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability

et al. 2016

View full text Add to dashboard Cite

Pseudouridylation is a common post-transcriptional modification in RNA, but its functional consequences at the cellular level remain largely unknown. Using a proximity-biotinylation assay, we identified a protein module in mitochondrial RNA granules, platforms for post-transcriptional RNA modification and ribosome assembly, containing several proteins of unknown function including three uncharacterized pseudouridine synthases, TRUB2, RPUSD3, and RPUSD4. TRUB2 and RPUSD4 were previously identified as core essential genes in CRISPR/Cas9 screens. Depletion of the individual enzymes produced specific mitochondrial protein synthesis and oxidative phosphorylation assembly defects without affecting mitochondrial mRNA levels. Investigation of the molecular targets in mitochondrial RNA by pseudouridine-Seq showed that RPUSD4 plays a role in the pseudouridylation of a single residue in the 16S rRNA, a modification that is essential for its stability and assembly into the mitochondrial ribosome, while TRUB2/RPUSD3 were similarly involved in pseudouridylating specific residues in mitochondrial mRNAs. These results establish essential roles for epitranscriptomic modification of mitochondrial RNA in mitochondrial protein synthesis, oxidative phosphorylation, and cell survival.

show abstract

“…One of the most abundant, ubiquitous, and highly conserved modifications is pseudouridine (psi or Ψ), an isomerization of uridine in which the C5 position, rather than the N1, is incorporated into the glycosidic bond (Cohn 1959(Cohn , 1960Scannell et al 1959;Yu and Allen 1959). This modification is found at high levels in rRNA in multiple organisms and is highly evolutionarily conserved at multiple sites in rRNA, tRNA, and spliceosomal RNA (Volkin and Cohn 1951;Spenkuch et al 2014;Li et al 2016). Most recently, with the advent of highthroughput sequencing tools, Ψ has also been found in mRNAs (Carlile et al 2014;Lovejoy et al 2014;Schwartz et al 2014;Li et al 2015).…”

Section: Introductionmentioning

confidence: 99%

mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii

Nakamoto

Lovejoy

Cygan

et al. 2017

RNA

View full text Add to dashboard Cite

RNA contains over 100 modified nucleotides that are created post-transcriptionally, among which pseudouridine (Ψ) is one of the most abundant. Although it was one of the first modifications discovered, the biological role of this modification is still not fully understood. Recently, we reported that a pseudouridine synthase (TgPUS1) is necessary for differentiation of the singlecelled eukaryotic parasite Toxoplasma gondii from active to chronic infection. To better understand the biological role of pseudouridylation, we report here gel-based and deep-sequencing methods to identify TgPUS1-dependent Ψ's in Toxoplasma RNA, and the use of TgPUS1 mutants to examine the effect of this modification on mRNAs. In addition to identifying conserved sites of pseudouridylation in Toxoplasma rRNA, tRNA, and snRNA, we also report extensive pseudouridylation of Toxoplasma mRNAs, with the Ψ's being relatively depleted in the 3 ′ ′ ′ ′ ′ -UTR but enriched at position 1 of codons. We show that many Ψ's in tRNA and mRNA are dependent on the action of TgPUS1 and that TgPUS1-dependent mRNA Ψ's are enriched in developmentally regulated transcripts. RNA-seq data obtained from wild-type and TgPUS1-mutant parasites shows that genes containing a TgPUS1-dependent Ψ are relatively more abundant in mutant parasites, while pulse/chase labeling of RNA with 4-thiouracil shows that mRNAs containing TgPUS1-dependent Ψ have a modest but statistically significant increase in half-life in the mutant parasites. These data are some of the first evidence suggesting that mRNA Ψ's play an important biological role.

show abstract

Pseudouridine: the fifth RNA nucleotide with renewed interests

Cited by 123 publications

References 57 publications

Comparative investigation into formycin A and pyrazofurin A biosynthesis reveals branch pathways for the construction ofC-nucleoside scaffolds

Comparative investigation into formycin A and pyrazofurin A biosynthesis reveals branch pathways for the construction ofC-nucleoside scaffolds

A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability

mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii

Contact Info

Product

Resources

About