4.5 Review

Deazaguanine derivatives, examples of crosstalk between RNA and DNA modification pathways

Journal

RNA BIOLOGY
Volume 14, Issue 9, Pages 1175-1184

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2016.1265200

Keywords

Deazaguanine modifications; DNA; tRNA

Funding

  1. National Institutes of Health [R01 GM70641]

Ask authors/readers for more resources

Seven-deazapurine modifications were thought to be highly specific of tRNAs, but have now been discovered in DNA of phages and of phylogenetically diverse bacteria, illustrating the plasticity of these modification pathways. The intermediate 7-cyano-7-deazaguanine (preQ(0)) is a shared precursor in the pathways leading to the insetion of 7-deazapurine derivatives in both tRNA and DNA. It is also used as an intermediate in the synthesis of secondary metabolites such as toyocamacin. The presence of 7-deazapurine in DNA is proposed to be a protection mechanism against endonucleases. This makes preQ0 a metabolite of underappreaciated but central importance.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Biochemistry & Molecular Biology

Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast

Leticia Pollo-Oliveira, Roland Klassen, Nick Davis, Akif Ciftci, Jo Marie Bacusmo, Maria Martinelli, Michael S. DeMott, Thomas J. Begley, Peter C. Dedon, Raffael Schaffrath, Valerie de Crecy-Lagard

BIOMOLECULES (2020)

Article Biochemistry & Molecular Biology

Reductive Evolution and Diversification of C5-Uracil Methylation in the Nucleic Acids of Mollicutes

Pascal Sirand-Pugnet, Damien Bregeon, Laure Beven, Catherine Goyenvalle, Alain Blanchard, Simon Rose, Henri Grosjean, Stephen Douthwaite, Djemel Hamdane, Valerie De Crecy-Lagard

BIOMOLECULES (2020)

Article Biochemistry & Molecular Biology

The DUF328 family member YaaA is a DNA-binding protein with a novel fold

Janani Prahlad, Yifeng Yuan, Jiusheng Lin, Chou-Wei Chang, Dirk Iwata-Reuyl, Yilun Liu, Valerie de Crecy-Lagard, Mark A. Wilson

JOURNAL OF BIOLOGICAL CHEMISTRY (2020)

Article Ecology

A network approach to elucidate and prioritize microbial dark matter in microbial communities

Tatyana Zamkovaya, Jamie S. Foster, Valerie de Crecy-Lagard, Ana Conesa

Summary: Microbial dark matter, consisting of unknown microbes, plays essential ecological roles and occupies top hubs within their communities. Excluding unknown taxa results in a reduction in network centrality measures, highlighting the importance of these unknown organisms.

ISME JOURNAL (2021)

Article Biochemistry & Molecular Biology

Pantoea Bacteriophage vB_PagS_MED16-A Siphovirus Containing a 2′-Deoxy-7-amido-7-deazaguanosine-Modified DNA

Monika Simoliuniene, Emilija Zukauskiene, Lidija Truncaite, Liang Cui, Geoffrey Hutinet, Darius Kazlauskas, Algirdas Kaupinis, Martynas Skapas, Valerie de Crecy-Lagard, Peter C. Dedon, Mindaugas Valius, Rolandas Meskys, Eugenijus Simoliunas

Summary: A novel siphovirus, MED16, was isolated and characterized, revealing 73 ORFs with 26 encoding unique proteins. Phylogenetic analysis placed MED16 in a new genus with siphovirus morphology. The study provides new insights into Pantoea-infecting viruses and diversity of DNA modifications in bacteriophages.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Biochemistry & Molecular Biology

Comparative Genomic Analysis of the DUF34 Protein Family Suggests Role as a Metal Ion Chaperone or Insertase

Colbie J. Reed, Geoffrey Hutinet, Valerie de Crecy-Lagard

Summary: Members of the DUF34 family, also known as the NIF3 protein superfamily, have been widely annotated as GTP cyclohydrolase I type 2, but new research suggests they may serve as metal ion insertases, chaperones, or metallocofactor maturases. This diverse molecular function could explain their involvement in pathways such as cell differentiation, metal ion homeostasis, pathogen virulence, redox, and universal stress responses.

BIOMOLECULES (2021)

Article Biochemistry & Molecular Biology

Epoxyqueuosine Reductase QueH in the Biosynthetic Pathway to tRNA Queuosine Is a Unique Metalloenzyme

Qiang Li, Remi Zallot, Brian S. MacTavish, Alvaro Montoya, Daniel J. Payan, You Hu, John A. Gerlt, Alexander Angerhofer, Valerie De Crecy-Lagard, Steven D. Bruner

Summary: This study reveals the final step of queuosine biosynthesis and demonstrates new diversity in the chemistry of iron/sulfur-dependent enzymes, providing novel insights into the mechanism of these widely conserved tRNA modifications.

BIOCHEMISTRY (2021)

Article Biochemistry & Molecular Biology

Dihydrouridine in the Transcriptome: New Life for This Ancient RNA Chemical Modification

Damien Bregeon, Ludovic Pecqueur, Sabrine Toubdji, Claudia Sudol, Murielle Lombard, Marc Fontecave, Valerie de Crecy-Lagard, Yuri Motorin, Mark Helm, Djemel Hamdane

Summary: Recent studies have revealed that RNA molecules undergo post-transcriptional modifications, including dihydrouridine modifications that were originally believed to be specific to tRNA. These modifications have been found not only in tRNA but also in mRNA, and they play important roles in meiotic chromosome segregation, protein translation rates, and cell proliferation. Dihydrouridine modifications are introduced by dihydrouridine synthases.

ACS CHEMICAL BIOLOGY (2022)

Article Biochemistry & Molecular Biology

Structural basis of Qng1-mediated salvage of the micronutrient queuine from queuosine-5′-monophosphate as the biological substrate

Shr-Hau Hung, Gregory Elliott, Thakku R. Ramkumar, Lyubomyr Burtnyak, Callum J. McGrenaghan, Sana Alkuzweny, Samia Quaiyum, Dirk Iwata-Reuyl, Xiaobei Pan, Brian D. Green, Vincent P. Kelly, Valerie De Crecy-Lagard, Manal A. Swairjo

Summary: Eukaryotic life relies on bacteria for the biosynthesis and supply of vitamins and micronutrients, including the micronutrient queuosine. The hydrolase enzyme QNG1 plays a crucial role in releasing queuine from queuosine-5'-monophosphate, which is essential for various physiological processes associated with queuine deficiency, such as metabolism, proliferation, differentiation, and cancer progression.

NUCLEIC ACIDS RESEARCH (2023)

Article Genetics & Heredity

Pyridoxal 5'-phosphate synthesis and salvage in Bacteria and Archaea: predicting pathway variant distributions and holes

Remi Denise, Jill Babor, John A. Gerlt, Valerie de Crecy-Lagard

Summary: Using a comparative genomic approach, the synthesis and salvage pathways of PLP were predicted in 5840 bacterial and archaeal species. It was found that many organisms lack key genes involved in PLP synthesis pathways, and further research is needed to identify potential transporters. This work provides a starting point for modeling the exchanges of B6 vitamers, predicting sensitivity to drugs targeting PLP synthesis enzymes, and addressing gaps in knowledge.

MICROBIAL GENOMICS (2023)

Article Biochemistry & Molecular Biology

Evolutionary Diversity of Dus2 Enzymes Reveals Novel Structural and Functional Features among Members of the RNA Dihydrouridine Synthases Family

Murielle Lombard, Colbie J. Reed, Ludovic Pecqueur, Bruno Faivre, Sabrine Toubdji, Claudia Sudol, Damien Bregeon, Valerie De Crecy-Lagard, Djemel Hamdane

Summary: Dihydrouridine (D) is a modified base found in tRNAs and recently detected in eukaryotic mRNAs, which plays a significant role in the conformational plasticity of RNA molecules. The study on the structure-function relationships of eukaryotic Dus proteins has been limited, but the study combining phylogenetic analysis and molecular modeling provides insights into the evolutionary molecular basis of D biosynthesis by these enzymes.

BIOMOLECULES (2022)

Article Microbiology

4?-Deoxypyridoxine disrupts vitamin B6 homeostasis in Escherichia coli K12 through combined inhibition of cumulative B6 uptake and PLP- dependent enzyme activity

Jill Babor, Angela Tramonti, Caterina Nardella, Adam Deutschbauer, Roberto Contestabile, Valerie de Crecy-Legard

Summary: Through exploring different conditions affecting PLP metabolism in E. coli K12, we discovered that 4dPN cannot be used as a source of vitamin B6 and exhibits toxicity in various conditions where B6 vitamin homeostasis is disrupted. The toxicity of 4dPN is likely due to the inhibition of PLP-dependent enzyme activity by 4'-deoxypyridoxine phosphate and interference with pyridoxine uptake. These toxic effects are dependent on the phosphorylation of 4dPN by pyridoxal kinase.

MICROBIOLOGY-SGM (2023)

Article Biochemistry & Molecular Biology

7-Deazaguanines in DNA: functional and structural elucidation of a DNA modification system

Samanthi Herath Gedara, Evan Wood, Andrew Gustafson, Cui Liang, Shr-Hau Hung, Joshua Savage, Phuc Phan, Amit Luthra, Valerie de Crecy-Lagard, Peter Dedon, Manal A. Swairjo, Dirk Iwata-Reuyl

Summary: This study reports the discovery of modified nucleosides in DNA and their association with the bacterial queuosine tRNA modification pathway and the dpd gene cluster. The roles and structures of each protein involved in this pathway are elucidated through in vitro reconstitution and X-ray crystallography. Unexpected activities in DpdA and DpdB are identified, including ATPase activity in DpdB and catalytically essential residues in DpdA. Additionally, the independent function of DpdC in DNA modification is demonstrated.

NUCLEIC ACIDS RESEARCH (2023)

Article Biochemistry & Molecular Biology

Four additional natural 7-deazaguanine derivatives in phages and how to make them

Liang Cui, Seetharamsing Balamkundu, Chuan-Fa Liu, Hong Ye, Jacob Hourihan, Astrid Rausch, Christopher Hauss, Emelie Nilsson, Matthias Hoetzinger, Karin Holmfeldt, Weijia Zhang, Laura Martinez-Alvarez, Xu Peng, Denise Tremblay, Sylvain Moinau, Natalie Solonenko, Matthew B. Sullivan, Yan-Jiun Lee, Andrew Mulholland, Peter R. Weigele, Valerie de Crecy-Lagard, Peter C. Dedon, Geoffrey Hutinet

Summary: Bacteriophages and bacteria constantly evolve new molecular tools in their arms race, and this study identifies various modifications of 7-deazaguanines and their related enzymes.

NUCLEIC ACIDS RESEARCH (2023)

Article Mathematical & Computational Biology

A roadmap for the functional annotation of protein families: a community perspective

Valerie de Crecy-Lagard, Rocio Amorin de Hegedus, Cecilia Arighi, Jill Babor, Alex Bateman, Ian Blaby, Crysten Blaby-Haas, Alan J. Bridge, Stephen K. Burley, Stacey Cleveland, Lucy J. Colwell, Ana Conesa, Christian Dallago, Antoine Danchin, Anita de Waard, Adam Deutschbauer, Raquel Dias, Yousong Ding, Gang Fang, Iddo Friedberg, John Gerlt, Joshua Goldford, Mark Gorelik, Benjamin M. Gyori, Christopher Henry, Geoffrey Hutinet, Marshall Jaroch, Peter D. Karp, Liudmyla Kondratova, Zhiyong Lu, Aron Marchler-Bauer, Maria-Jesus Martin, Claire McWhite, Gaurav D. Moghe, Paul Monaghan, Anne Morgat, Christopher J. Mungall, Darren A. Natale, William C. Nelson, Sean O'Donoghue, Christine Orengo, Katherine H. O'Toole, Predrag Radivojac, Colbie Reed, Richard J. Roberts, Dmitri Rodionov, Irina A. Rodionova, Jeffrey D. Rudolf, Lana Saleh, Gloria Sheynkman, Francoise Thibaud-Nissen, Paul D. Thomas, Peter Uetz, David Vallenet, Erica Watson Carter, Peter R. Weigele, Valerie Wood, Elisha M. Wood-Charlson, Jin Xu

Summary: In the past 25 years, biology has entered the genomic era and has become a science of 'big data'. However, accurate functional annotations of the proteins encoded by sequenced genomes are lacking, with only about half of the predicted proteins having accurate annotations. This gap in knowledge hampers the progress of biological research. To address this issue, a brainstorming meeting funded by the National Science Foundation was held in February 2022, bringing together data scientists, biocurators, computational biologists, and experimentalists to comprehensively assess the current state of functional annotations of protein families and propose solutions to move forward.

DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION (2022)

No Data Available