Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA folding studies inside peptide-rich droplets reveal roles of modified nucleosides at the origin of life.

ABSTRACT: Compartmentalization of RNA in biopolymer-rich membraneless organelles is now understood to be pervasive and critical for the function of extant biology and has been proposed as a prebiotically plausible way to accumulate RNA. However, compartment-RNA interactions that drive encapsulation have the potential to influence RNA structure and function in compartment- and RNA sequence-dependent ways. Here, we detail next-generation sequencing (NGS) experiments performed in membraneless compartments called complex coacervates to characterize the fold of many different transfer RNAs (tRNAs) simultaneously under the potentially denaturing conditions of these compartments. Notably, we find that natural modifications favor the native fold of tRNAs in these compartments. This suggests that covalent RNA modifications could have played a critical role in metabolic processes at the origin of life.

SUBMITTER: Meyer MO

PROVIDER: S-EPMC10511188 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

RNA folding studies inside peptide-rich droplets reveal roles of modified nucleosides at the origin of life.

Meyer McCauley O MO Yamagami Ryota R Choi Saehyun S Keating Christine D CD Bevilacqua Philip C PC

Science advances 20230920 38

Compartmentalization of RNA in biopolymer-rich membraneless organelles is now understood to be pervasive and critical for the function of extant biology and has been proposed as a prebiotically plausible way to accumulate RNA. However, compartment-RNA interactions that drive encapsulation have the potential to influence RNA structure and function in compartment- and RNA sequence-dependent ways. Here, we detail next-generation sequencing (NGS) experiments performed in membraneless compartments ca ...[more]

PMID: 37729412

Similar Datasets

tRNA structure-seq in peptide-rich droplets

Project description:Compartmentalization of RNA in biopolymer-rich membraneless organelles is now understood to be pervasive and critical for the function of extant biology, and has been proposed as a prebiotically-plausible way to accumulate RNA. Compartment-RNA interactions that drive encapsulation have the potential to influence RNA structure and function in compartment- and RNA sequence-dependent ways. Herein, we detail Next-Generation Sequencing (NGS) experiments performed for the first time in membraneless compartments called complex coacervates to characterize the fold of many different transfer RNAs (tRNAs) simultaneously under the potentially denaturing conditions of these compartments. Transfer RNAs are essential for protein synthesis and predate the last universal common ancestor (LUCA) of all organisms, making them relevant to both extant and ancient biology. Since tRNAs are the most heavily modified RNAs known, with modifications crucial to RNA structure, function, and gene regulation, we also compared unmodified and naturally-modified tRNAs. We elucidate the effects of Mg2+ concentration, polyion charge ratio, and polyion length on tRNA structures. The approach herein, which can be applied to study other RNAs in diverse condensates, reveals that RNA can achieve native tertiary structure in a robust fashion in membraneless compartments. Strikingly, we find that natural modifications favor the native fold of tRNAs in these compartments. This suggests that modifications could have played a critical role in metabolic processes at the origin of life.

2023-09-27 | GSE225730 | GEO

tRNA structure-seq in peptide-rich droplets

Project description:tRNA structure-seq in peptide-rich droplets

| PRJNA937237 | ENA

Atomistic Peptide Folding Simulations Reveal Interplay of Entropy and Long-Range Interactions in Folding Cooperativity.

Project description:Understanding how proteins fold has remained a problem of great interest in biophysical research. Atomistic computer simulations using physics-based force fields can provide important insights on the interplay of different interactions and energetics and their roles in governing the folding thermodynamics and mechanism. In particular, generalized Born (GB)-based implicit solvent force fields can be optimized to provide an appropriate balance between solvation and intramolecular interactions and successfully recapitulate experimental conformational equilibria for a set of helical and β-hairpin peptides. Here, we further demonstrate that key thermodynamic properties and their temperature dependence obtained from replica exchange molecular dynamics simulations of these peptides are in quantitative agreement with experimental results. Useful lessons can be learned on how the interplay of entropy and sequentially long-range interactions governs the mechanism and cooperativity of folding. These results highlight the great potential of high-quality implicit solvent force fields for studying protein folding and large-scale conformational transitions.

| S-EPMC6135771 | biostudies-literature

Identification and quantification of modified nucleosides in Saccharomyces cerevisiae mRNAs

Project description:Post-transcriptional modifications to messenger RNAs (mRNAs) have the potential to alter the biological function of this important class of biomolecules. The study of mRNA modifications is a rapidly emerging field, and the full complement of chemical modifications in mRNAs is not yet established. We sought to identify and quantify the modifications present in yeast mRNAs using an ultra-high performance liquid chromatography tandem mass spectrometry method to detect 40 nucleoside variations in parallel. We observe six modified nucleosides with high confidence in highly purified mRNA samples (N7-methylguanosine, N6-methyladenosine, 2’-O-methylguanosine, 2’-O-methylcytidine, N4-acetylcytidine and 5-formylcytidine), and identify the yeast protein responsible for N4-acetylcytidine incorporation in mRNAs, Rra1. Additionally, we find that mRNA modification levels change in response to heat shock, glucose starvation and/or oxidative stress. This work expands the repertoire of potential chemical modifications in mRNAs, and highlights the value of integrating mass spectrometry tools in the mRNA modification discovery and characterization pipeline.

2019-06-20 | GSE126405 | GEO

Sample preconcentration inside sessile droplets using electrowetting.

Project description:Electrowetting with alternate voltage (AC) creates azimuthal flow vortices inside sessile droplets. These flow vortices can be controlled by introducing pinning sites at the contact line. When the frequency of the applied AC voltage is gradually ramped from a few hundreds of hertz to a few tens of kilohertz the azimuthal flow vortices contract and move towards the contact line near the pinning site. Dispersed particles in the liquid are collected in the center of these vortices leading to an increase in the local particle concentration by up to more than one order of magnitude. We provide a qualitative explanation for symmetry of the flow patterns within the drops and discuss possible scenarios explaining the particle collection and preconcentration.

| S-EPMC3724702 | biostudies-other

Origin of Increased Solvent Accessibility of Peptide Bonds in Mutual Synergetic Folding Proteins.

Project description:Mutual Synergetic Folding (MSF) proteins belong to a recently discovered class of proteins. These proteins are disordered in their monomeric but ordered in their oligomeric forms. Their amino acid composition is more similar to globular proteins than to disordered ones. Our preceding work shed light on important structural aspects of the structural organization of these proteins, but the background of this behavior is still unknown. We suggest that solvent accessibility is an important factor, especially solvent accessibility of the peptide bonds can be accounted for this phenomenon. The side chains of the amino acids which form a peptide bond have a high local contribution to the shielding of the peptide bond from the solvent. During the oligomerization step, other non-local residues contribute to the shielding. We investigated these local and non-local effects of shielding based on Shannon information entropy calculations. We found that MSF and globular homodimeric proteins have different local contributions resulting from different amino acid pair frequencies. Their non-local distribution is also different because of distinctive inter-subunit contacts.

| S-EPMC8704591 | biostudies-literature

Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles.

Project description:Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems.

| S-EPMC9026255 | biostudies-literature

Roles of beta-turns in protein folding: from peptide models to protein engineering.

Project description:Reverse turns are a major class of protein secondary structure; they represent sites of chain reversal and thus sites where the globular character of a protein is created. It has been speculated for many years that turns may nucleate the formation of structure in protein folding, as their propensity to occur will favor the approximation of their flanking regions and their general tendency to be hydrophilic will favor their disposition at the solvent-accessible surface. Reverse turns are local features, and it is therefore not surprising that their structural properties have been extensively studied using peptide models. In this article, we review research on peptide models of turns to test the hypothesis that the propensities of turns to form in short peptides will relate to the roles of corresponding sequences in protein folding. Turns with significant stability as isolated entities should actively promote the folding of a protein, and by contrast, turn sequences that merely allow the chain to adopt conformations required for chain reversal are predicted to be passive in the folding mechanism. We discuss results of protein engineering studies of the roles of turn residues in folding mechanisms. Factors that correlate with the importance of turns in folding indeed include their intrinsic stability, as well as their topological context and their participation in hydrophobic networks within the protein's structure.

| S-EPMC2904567 | biostudies-literature

DNA-Modified Liquid Crystal Droplets.

Project description:In this work, we have combined the advantages of sequence programmability of DNA nanotechnology and optical birefringence of liquid crystals (LCs). Herein, DNA amphiphiles were adsorbed onto LC droplets. A unique phenomenon of LC droplet aggregation was demonstrated, using DNA-modified LC droplets, through complementary DNA hybridization. Further functionalization of DNA-modified LC droplets with a desired DNA sequence was used to detect a wide range of chemicals and biomolecules, such as Hg2+, thrombin, and enzymes, through LC droplet aggregation and vice versa, which can be seen through the naked eye. These DNA-modified LC droplets can be printed onto a desired patterned surface with temperature-induced responsiveness and reversibility. Overall, our work is the first to report DNA-modified LC droplet, which provides a general detection platform based on the development of DNA aptamers. Additionally, this work inspires the exploration of surface information visualization combined with microcontact printing.

| S-EPMC9138460 | biostudies-literature

The Signature of Serum Modified Nucleosides in Uveitis.

Project description:PurposeThis study aims to evaluate the metabolism of serum-modified nucleosides in uveitis by using liquid chromatography-tandem mass spectrometry (LC-MS) and to develop potential diagnostic biomarkers for uveitis.MethodsForty-two patients with different subtypes of uveitis (idiopathic uveitis, Vogt-Koyanagi-Harada [VKH] disease, and ankylosing spondylitis [AS]) and 32 healthy controls were recruited in this retrospective case-control study. The concentrations of 23 modified nucleosides in patient serum were quantified by LC-MS. The data was statistically analyzed with SPSS and GraphPad Prism.ResultsThe data revealed that 13 out of 23 modified nucleosides (m6A, m1A, m6Am, Cm, ac4C, Gm, m1G, m2G, m2,2G, Um, m3U, m5U, and m5Um) effectively showed quantifiable chromatographic peaks. The statistical results indicated that there were extremely significant differences for m2G, Gm, Cm, and m1G between healthy controls and uveitis patients. The differences for Gm, m6A,and m5U were able to further assort idiopathic uveitis and uveitis with systemic inflammation including VKH and AS. Interestingly, each specific subtype of uveitis is characterized by its signature combination of serum-modified nucleotides comparing with healthy controls.ConclusionsThis study revealed that the metabolism of serum-modified nucleosides in uveitis patients display significant differences from healthy controls. The signature combination of serum modified nucleotides for each subtype of uveitis may be applied for the potential diagnosis of uveitis.

| S-EPMC11875031 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data