Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion

ACS Nano, Journal Year: 2022, Volume and Issue: 16(12), P. 20163 - 20173

Published: Dec. 13, 2022

Lipid nanoparticles (LNPs) have emerged as potent carriers for mRNA delivery, but several challenges remain before this approach can offer broad clinical translation of therapeutics. To improve their efficacy, a better understanding is required regarding how LNPs are trapped and processed at the anionic endosomal membrane prior to release. We used surface-sensitive fluorescence microscopy with single LNP resolution investigate pH dependency binding kinetics ionizable lipid-containing supported model membrane. A sharp increase was observed when lowered from 6 5, accompanied by stepwise large-scale disintegration. For preincubated in serum, protein corona formation shifted onset subsequent disintegration lower pH, an effect that less pronounced lipoprotein-depleted serum. The mimic eventually become severely limited suppression driving force multivalent bonds during attachment or, more specifically, charge neutralization lipids due association cationic earlier attached upon Cell uptake experiments demonstrated marginal differences untreated whereas serum increased mRNA-controlled (eGFP) production substantially. This complies data suggests on surface influences nature interaction between membranes.

Language: Английский

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The Role of DEAD-Box ATPases in Gene Expression and the Regulation of RNA–Protein Condensates

Annual Review of Biochemistry, Journal Year: 2022, Volume and Issue: 91(1), P. 197 - 219

Published: March 19, 2022

DEAD-box ATPases constitute a very large protein family present in all cells, often great abundance. From bacteria to humans, they play critical roles many aspects of RNA metabolism, and due their widespread importance biology, have been characterized detail at both the structural biochemical levels. proteins function as RNA-dependent that can unwind short duplexes RNA, remodel ribonucleoprotein (RNP) complexes, or act clamps promote RNP assembly. Yet, it remains enigmatic how individual mechanistically contribute specific RNA-processing steps. Here, we review role regulation gene expression propose one common these enzymes is liquid-liquid phase separation condensates.

Language: Английский

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Multiple Roles of PLK1 in Mitosis and Meiosis

Cells, Journal Year: 2023, Volume and Issue: 12(1), P. 187 - 187

Published: Jan. 2, 2023

Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators checkpoint to ensure the proper progression division. A key regulator division is polo-like kinase 1 (PLK1), member serine/threonine family plays an important role in regulating mitotic meiotic cycle. The phosphorylation specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, spindle assembly, chromosome segregation, cytokinesis. In mammalian oogenesis, essential for resuming meiosis before ovulation establishing spindle. Among other potential roles, regulates localized translation spindle-enriched mRNAs phosphorylating thereby inhibiting translational repressor 4E-BP1, downstream target mTOR (mammalian rapamycin) pathway. this review, we summarize functions mitosis, meiosis, cytokinesis focus on mRNA translation. However, knowledge regulation remains limited.

Language: Английский

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Chloroplast Proteostasis: Import, Sorting, Ubiquitination, and Proteolysis

Annual Review of Plant Biology, Journal Year: 2023, Volume and Issue: 74(1), P. 259 - 283

Published: March 1, 2023

Chloroplasts are the defining plant organelles with responsibility for photosynthesis and other vital functions. To deliver these functions, they possess a complex proteome comprising thousands of largely nucleus-encoded proteins. Composition is controlled by diverse processes affecting protein translocation degradation—our focus here. Most chloroplast proteins imported from cytosol via multiprotein translocons in outer inner envelope membranes (the TOC TIC complexes, respectively), or one several noncanonical pathways, then sorted different systems to organellar subcompartments. Chloroplast proteolysis equally complex, involving concerted action internal proteases prokaryotic origin nucleocytosolic ubiquitin–proteasome system (UPS). The UPS degrades unimported chloroplast-resident chloroplast-associated degradation (CHLORAD). latter targets apparatus regulate import, as well numerous directly, reconfigure functions response developmental environmental signals.

Language: Английский

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The Rab5 effector FERRY links early endosomes with mRNA localization

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(11), P. 1839 - 1855.e13

Published: June 1, 2023

Localized translation is vital to polarized cells and requires precise robust distribution of different mRNAs ribosomes across the cell. However, underlying molecular mechanisms are poorly understood important players lacking. Here, we discovered a Rab5 effector, five-subunit endosomal RNA/ribosome intermediary (FERRY) complex, that recruits early endosomes through direct mRNA-interaction. FERRY displays preferential binding certain groups transcripts, including encoding mitochondrial proteins. Deletion subunits reduces localization transcripts in has significant impact on mRNA levels. Clinical studies show genetic disruption causes severe brain damage. We found that, neurons, co-localizes with endosomes, loaded FERRY-positive close proximity mitochondria. thus transforms into carriers plays key role regulating transport.

Language: Английский

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Maintenance of a short-lived protein required for long-term memory involves cycles of transcription and local translation

Neuron, Journal Year: 2023, Volume and Issue: 111(13), P. 2051 - 2064.e6

Published: April 25, 2023

Language: Английский

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The Role of PGC-1α-Mediated Mitochondrial Biogenesis in Neurons

Neurochemical Research, Journal Year: 2023, Volume and Issue: 48(9), P. 2595 - 2606

Published: April 25, 2023

Language: Английский

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Lost in local translation: TDP-43 and FUS in axonal/neuromuscular junction maintenance and dysregulation in amyotrophic lateral sclerosis

Neuron, Journal Year: 2023, Volume and Issue: 111(9), P. 1355 - 1380

Published: March 23, 2023

Language: Английский

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DeepLocRNA: an interpretable deep learning model for predicting RNA subcellular localization with domain-specific transfer-learning

Bioinformatics, Journal Year: 2024, Volume and Issue: 40(2)

Published: Feb. 1, 2024

Accurate prediction of RNA subcellular localization plays an important role in understanding cellular processes and functions. Although post-transcriptional are governed by trans-acting binding proteins (RBPs) through interaction with cis-regulatory motifs, current methods do not incorporate RBP-binding information.

Language: Английский

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Differentially expressed messenger RNA isoforms in beef cattle skeletal muscle with different fatty acid profiles

Meat Science, Journal Year: 2025, Volume and Issue: 222, P. 109751 - 109751

Published: Jan. 7, 2025

Language: Английский

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