scholarly journals Prebiotically Plausible “Patching” of RNA Backbone Cleavage through a 3′–5′ Pyrophosphate Linkage

2019 ◽  
Vol 141 (45) ◽  
pp. 18104-18112 ◽  
Author(s):  
Tom H. Wright ◽  
Constantin Giurgiu ◽  
Wen Zhang ◽  
Aleksandar Radakovic ◽  
Derek K. O’Flaherty ◽  
...  
Keyword(s):  
Backbone Cleavage ◽  
Rna Backbone

scholarly journals Prebiotically Plausible ‘Patching’ of RNA Backbone Cleavage Through a 3′-5′ Pyrophosphate Linkage

2019 ◽  
Author(s):  
Tom H. Wright ◽  
Constantin Giurgiu ◽  
Aleksandar Radakovic ◽  
Derek K. O’Flaherty ◽  
Lijun Zhou ◽  
...  
Keyword(s):  
Genetic Information ◽  
Prebiotic Chemistry ◽  
Rna World ◽  
Rna Replication ◽  
Cellular Biology ◽  
Backbone Cleavage ◽  
Phosphodiester Backbone ◽  
Rna Backbone ◽  
Multiple Cycles ◽  
The Stability

ABSTRACTAchieving multiple cycles of RNA replication within a model protocell would be a critical step towards demonstrating a path from prebiotic chemistry to cellular biology. Any model for early life based on an ‘RNA world’ must account for RNA strand cleavage and hydrolysis, which would degrade primitive genetic information and lead to an accumulation of truncated, phosphate-terminated strands. We show here that cleavage of the phosphodiester backbone is not an endpoint for RNA replication. Instead, 3′ -phosphate terminated RNA strands are able to participate in template-directed copying reactions with activated ribonucleotide monomers. These reactions form a pyrophosphate linkage, the stability of which we have characterized in the context of RNA copying chemistry. We found that the pyrophosphate bond is relatively stable within an RNA duplex and in the presence of chelated magnesium. Under these conditions, pyrophosphate-RNA can act as a temporary ‘patch’ to template the polymerization of canonical ribonucleotides, suggesting a plausible non-enzymatic pathway for the salvage and recovery of genetic information following strand cleavage.

Novel Biodegradable Polymer with Redox‐Triggered Backbone Cleavage Through Sequential 1,6‐Elimination and 1,5‐Cyclization Reactions

2017 ◽  
Vol 38 (19) ◽  
pp. 1700395 ◽  
Author(s):  
Chang‐Hee Whang ◽  
Kyeong Soo Kim ◽  
Jungeun Bae ◽  
Jun Chen ◽  
Ho‐Wook Jun ◽  
...  
Keyword(s):  
Biodegradable Polymer ◽  
Backbone Cleavage ◽  
Cyclization Reactions

Characterization of a Backbone Cleavage Product of BMS-196854 (Oncostatin M), a Recombinant Anti-inflammatory Cytokine

2001 ◽  
Vol 6 (2) ◽  
pp. 255-261 ◽  
Author(s):  
Fang Zhao ◽  
Daniel J. Stein ◽  
Mehdi Paborji ◽  
Patricia W. Cash ◽  
Barbara J. Root ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Cleavage Product ◽  
Oncostatin M ◽  
Backbone Cleavage ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Disulfide bridge cross-linking between protein and the RNA backbone as a tool to study RNase H1

2020 ◽  
Vol 28 (23) ◽  
pp. 115741
Author(s):  
Malwina Hyjek-Składanowska ◽  
Anna R. Stasińska ◽  
Agnieszka Napiórkowska-Gromadzka ◽  
Aneta Bartłomiejczak ◽  
Punit P. Seth ◽  
...  
Keyword(s):  
Disulfide Bridge ◽  
Cross Linking ◽  
Rna Backbone

scholarly journals A deep learning framework to predict binding preference of RNA constituents on protein surface

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jordy Homing Lam ◽  
Yu Li ◽  
Lizhe Zhu ◽  
Ramzan Umarov ◽  
Hanlun Jiang ◽  
...  
Keyword(s):  
Deep Learning ◽  
Protein Structure ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Preference ◽  
Rna Backbone ◽  
Binding Pockets ◽  
Rna Interaction

Abstract Protein-RNA interaction plays important roles in post-transcriptional regulation. However, the task of predicting these interactions given a protein structure is difficult. Here we show that, by leveraging a deep learning model NucleicNet, attributes such as binding preference of RNA backbone constituents and different bases can be predicted from local physicochemical characteristics of protein structure surface. On a diverse set of challenging RNA-binding proteins, including Fem-3-binding-factor 2, Argonaute 2 and Ribonuclease III, NucleicNet can accurately recover interaction modes discovered by structural biology experiments. Furthermore, we show that, without seeing any in vitro or in vivo assay data, NucleicNet can still achieve consistency with experiments, including RNAcompete, Immunoprecipitation Assay, and siRNA Knockdown Benchmark. NucleicNet can thus serve to provide quantitative fitness of RNA sequences for given binding pockets or to predict potential binding pockets and binding RNAs for previously unknown RNA binding proteins.

scholarly journals Adaptation of Syntenic Xyloglucan Utilization Loci of Human Gut Bacteroidetes to Polysaccharide Side Chain Diversity

2019 ◽  
Vol 85 (20) ◽  
Author(s):  
Guillaume Déjean ◽  
Alexandra S. Tauzin ◽  
Stuart W. Bennett ◽  
A. Louise Creagh ◽  
Harry Brumer
Keyword(s):  
Gut Microbiota ◽  
Community Dynamics ◽  
Gene Clusters ◽  
Individual Species ◽  
Glycoside Hydrolase Family ◽  
Backbone Cleavage ◽  
Structural Variations ◽  
Human Gut ◽  
Complex Carbohydrates

ABSTRACT Genome sequencing has revealed substantial variation in the predicted abilities of individual species within animal gut microbiota to metabolize the complex carbohydrates comprising dietary fiber. At the same time, a currently limited body of functional studies precludes a richer understanding of how dietary glycan structures affect the gut microbiota composition and community dynamics. Here, using biochemical and biophysical techniques, we identified and characterized differences among recombinant proteins from syntenic xyloglucan utilization loci (XyGUL) of three Bacteroides and one Dysgonomonas species from the human gut, which drive substrate specificity and access to distinct polysaccharide side chains. Enzymology of four syntenic glycoside hydrolase family 5 subfamily 4 (GH5_4) endo-xyloglucanases revealed surprising differences in xyloglucan (XyG) backbone cleavage specificity, including the ability of some homologs to hydrolyze congested branched positions. Further, differences in the complement of GH43 alpha-l-arabinofuranosidases and GH95 alpha-l-fucosidases among syntenic XyGUL confer distinct abilities to fully saccharify plant species-specific arabinogalactoxyloglucan and/or fucogalactoxyloglucan. Finally, characterization of highly sequence-divergent cell surface glycan-binding proteins (SGBPs) across syntenic XyGUL revealed a novel group of XyG oligosaccharide-specific SGBPs encoded within select Bacteroides. IMPORTANCE The catabolism of complex carbohydrates that otherwise escape the endogenous digestive enzymes of humans and other animals drives the composition and function of the gut microbiota. Thus, detailed molecular characterization of dietary glycan utilization systems is essential both to understand the ecology of these complex communities and to manipulate their compositions, e.g., to benefit human health. Our research reveals new insight into how ubiquitous members of the human gut microbiota have evolved a set of microheterogeneous gene clusters to efficiently respond to the structural variations of plant xyloglucans. The data here will enable refined functional prediction of xyloglucan utilization among diverse environmental taxa in animal guts and beyond.

scholarly journals The effect of adenine protonation on RNA phosphodiester backbone bond cleavage elucidated by deaza-nucleobase modifications and mass spectrometry

2019 ◽  
Vol 47 (14) ◽  
pp. 7223-7234 ◽  
Author(s):  
Elisabeth Fuchs ◽  
Christoph Falschlunger ◽  
Ronald Micura ◽  
Kathrin Breuker
Keyword(s):  
Mass Spectrometry ◽  
Gas Phase ◽  
Vibrational Excitation ◽  
Bond Cleavage ◽  
Low Energy ◽  
Biological Processes ◽  
Phosphodiester Backbone ◽  
Collisionally Activated Dissociation ◽  
Rna Backbone ◽  
Ionic Hydrogen Bonds

Abstract The catalytic strategies of small self-cleaving ribozymes often involve interactions between nucleobases and the ribonucleic acid (RNA) backbone. Here we show that multiply protonated, gaseous RNA has an intrinsic preference for the formation of ionic hydrogen bonds between adenine protonated at N3 and the phosphodiester backbone moiety on its 5′-side that facilitates preferential phosphodiester backbone bond cleavage upon vibrational excitation by low-energy collisionally activated dissociation. Removal of the basic N3 site by deaza-modification of adenine was found to abrogate preferential phosphodiester backbone bond cleavage. No such effects were observed for N1 or N7 of adenine. Importantly, we found that the pH of the solution used for generation of the multiply protonated, gaseous RNA ions by electrospray ionization affects phosphodiester backbone bond cleavage next to adenine, which implies that the protonation patterns in solution are at least in part preserved during and after transfer into the gas phase. Our study suggests that interactions between protonated adenine and phosphodiester moieties of RNA may play a more important mechanistic role in biological processes than considered until now.

scholarly journals Effects of Cold Jet Atmospheric Pressure Plasma on the Structural Characteristics and Immunoreactivity of Celiac-Toxic Peptides and Wheat Storage Proteins

2020 ◽  
Vol 21 (3) ◽  
pp. 1012
Author(s):  
Fusheng Sun ◽  
Xiaoxue Xie ◽  
Yufan Zhang ◽  
Jiangwei Duan ◽  
Mingyu Ma ◽  
...  
Keyword(s):  
Atmospheric Pressure ◽  
Storage Proteins ◽  
Structural Characteristics ◽  
Atmospheric Pressure Plasma ◽  
High Energy ◽  
Backbone Cleavage ◽  
Excited Atoms ◽  
Wheat Storage Proteins ◽  
Toxic Peptides

The present research reported the effects of structural properties and immunoreactivity of celiac-toxic peptides and wheat storage proteins modified by cold jet atmospheric pressure (CJAP) plasma. It could generate numerous high-energy excited atoms, photons, electrons, and reactive oxygen and nitrogen species, including O3, H2O2, •OH, NO2− and NO3− etc., to modify two model peptides and wheat storage proteins. The Orbitrap HR-LC-MS/MS was utilized to identify and quantify CJAP plasma-modified model peptide products. Backbone cleavage of QQPFP and PQPQLPY at specific proline and glutamine residues, accompanied by hydroxylation at the aromatic ring of phenylalanine and tyrosine residues, contributed to the reduction and modification of celiac-toxic peptides. Apart from fragmentation, oxidation, and agglomeration states were evaluated, including carbonyl formation and the decline of γ-gliadin. The immunoreactivity of gliadin extract declined over time, demonstrating a significant decrease by 51.95% after 60 min of CJAP plasma treatment in vitro. The CJAP plasma could initiate depolymerization of gluten polymer, thereby reducing the amounts of large-sized polymers. In conclusion, CJAP plasma could be employed as a potential technique in the modification and reduction of celiac-toxic peptides and wheat storage proteins.

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