Lipid membranes modulate the activity of RNA through sequence-dependent interactions

Czerniak, Tomasz; Sáenz, James

doi:10.1073/pnas.2119235119

Cited by 34 publications

(36 citation statements)

References 75 publications

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“…7). The inhibitory effects of high lipid concentrations on catalytic RNA activity has been recently reported, concluding that the ratio of RNA to lipids as well as RNA sequence and length determine RNA-lipid interactions and, consequently, how ribozyme activity is modulated (enhancement or inhibition) 27 . The increase in overall ligation yields at higher RNA concentrations can therefore be explained by a mitigation of both of these effects.…”

Section: Resultsmentioning

confidence: 99%

Exchange, catalysis and amplification of encapsulated RNA driven by periodic temperature changes

Salibi

Peter

Schwille

et al. 2022

Preprint

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Growth and division of biological cells is based on the complex orchestration of spatiotemporally controlled reactions driven by highly evolved proteins. In contrast, it remains unknown how their primordial predecessors could achieve a stable inheritance of cytosolic components before the advent of translation. An attractive scenario assumes that periodic changes of environmental conditions acted as pacemakers for the proliferation of early protocells. Using catalytic RNA (ribozymes) as models for primitive biocatalytic molecules, we demonstrate that the repeated freezing and thawing of aqueous solutions enables the assembly of active ribozymes from inactive precursors encapsulated in separate lipid vesicle populations. Furthermore, we show that encapsulated ligase ribozymes can overcome freezing-induced content loss and successive dilution by freeze-thaw driven propagation in feedstock vesicles. Thus, cyclic freezing and melting of aqueous solvents – a plausible physicochemical driver likely present on early Earth – provides a simple scenario that uncouples compartment growth and division from nucleic acid self-replication, while maintaining the propagation of these replicators inside new vesicle populations.

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Section: Resultsmentioning

confidence: 99%

Exchange, catalysis and amplification of encapsulated RNA driven by periodic temperature changes

Salibi

Peter

Schwille

et al. 2022

Preprint

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“…One mechanism by which these motifs could act is to modulate direct RNA interaction with lipid membranes during biogenesis (Figure 2b). Czerniak and Saenz (2022) recently demonstrated that RNA oligomer binding is highly dependent on membrane fluidity, and thus differential lipid content. Indeed, earlier work by Janas et al (2012) found that increased sphingomyelin/cholesterol content of liposomes (lipids enriched within raft regions in EVs), showed increased binding of tRNA Sec .…”

Section:  Ev-enriched Rna Sequence Motifsmentioning

confidence: 99%

Unpacking extracellular vesicles: RNA cargo loading and function

Dellar

Hill

Melling

et al. 2022

J of Extracellular Bio

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Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed structures produced by prokaryotic and eukaryotic cells. EVs carry a range of biological cargoes, including RNA, protein, and lipids, which may have both metabolic significance and signalling potential. EV release has been suggested to play a critical role in maintaining intracellular homeostasis by eliminating unnecessary biological material from EV producing cells, and as a delivery system to enable cellular communication between both neighbouring and distant cells without physical contact. In this review, we give an overview of what is known about the relative enrichment of the different types of RNA that have been associated with EVs in the most recent research efforts. We then examine the selective and non-selective incorporation of these different RNA biotypes into EVs, the molecular systems of RNA sorting into EVs that have been elucidated so far, and the role of this process in EV-producing cells. Finally, we also discuss the model systems providing evidence for EV-mediated delivery of RNA to recipient cells, and the implications of this evidence for the relevance of this RNA delivery process in both physiological and pathological scenarios.

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“…Another mechanism by which lipids directly act with RNA is through lipid membrane binding with RNA through G-quadruplex formation and riboregulation of guanine residues in short RNAs, which are dependent upon RNA nucleotide content, base pairing, and length. 18 The lipid-RNA interaction and modification of ribozyme activity occur on the lipid membrane as synthetic riboswitches and RNA-based lipid biosensors. Different from lipid-DNA complexes, lipid-transfer RNA (tRNA) complexes play critical roles in the maintenance of tRNA folding status, aggregation, stability, and condensation and are dependent on lipid metabolite chemical properties, concentrations, binding locations, and action duration.…”

Section: Lipids and Genes: Regulatory Roles Of Lipids In Rna Expressionmentioning

confidence: 99%

“…Another mechanism by which lipids directly act with RNA is through lipid membrane binding with RNA through G‐quadruplex formation and riboregulation of guanine residues in short RNAs, which are dependent upon RNA nucleotide content, base pairing, and length 18 . The lipid‐RNA interaction and modification of ribozyme activity occur on the lipid membrane as synthetic riboswitches and RNA‐based lipid biosensors.…”

mentioning

confidence: 99%

Lipids and Genes: Regulatory roles of lipids in RNA expression

Wang

Han

Powell

2022

Clinical and Translational Dis

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Nuclear lipid metabolism and metabolites play important roles in the regulation of lipid‐lipid, lipid‐gene, lipid‐chromatin, lipid‐membrane, and lipid‐protein interactions to maintain the nuclear microenvironment, three‐dimensional chromatin architecture, gene expression and transcription, and biological function. This editorial highlights the value of lipid‐gene in the identification and development of biomarkers and targets and emphasises the significance of interregulation between lipids and genes in the innovation and application of precise therapies for patients. Regulatory functions of nuclear lipid dynamics and biophysics modify transcriptomic expression, and modification (lipotranscriptome) can be a new approach for discovery and development of disease‐specific diagnoses and therapies, although there are several challenges to be overcome. A better understanding of how lipid‐based changes in nuclear functions and transcriptomic profiles modify clinical phenomes will provide new insights to understand the molecular mechanisms of diseases and to develop spatiotemporal molecular medicine diagnostics and therapeutics.

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Lipid membranes modulate the activity of RNA through sequence-dependent interactions

Cited by 34 publications

References 75 publications

Exchange, catalysis and amplification of encapsulated RNA driven by periodic temperature changes

Exchange, catalysis and amplification of encapsulated RNA driven by periodic temperature changes

Unpacking extracellular vesicles: RNA cargo loading and function

Lipids and Genes: Regulatory roles of lipids in RNA expression

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