RNA binding proteins: Diversity from microsurgeons to cowboys

Oroz, Javier; Laurents, Douglas V.

doi:10.1016/j.bbagrm.2019.06.009

Cited by 3 publications

(4 citation statements)

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“…Currently, molecular mechanisms of exosomal RNA sorting are not completely clear. In general, many aspects of RNA biology including RNA distribution and trafficking depend on interactions with multitude of RNA-binding proteins (RBP) [ 49 , 50 ]. Various RBPs constitute up to 25% of exosomal protein content [ 51 ].…”

Section: Biogenesis Release and Uptake Of Exosomesmentioning

confidence: 99%

Exosomes as Natural Nanocarriers for RNA-Based Therapy and Prophylaxis

et al. 2022

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Exosomes are natural nanocontainers actively secreted by the body’s cells and transmitting molecular signals of various types to recipient cells. Cellular mechanisms of exosomes’ biogenesis involve specific sorting of RNA for incorporation into them. As a result, the molecular composition of exosomes is closely related to the donor cell’s functional state, and this makes exosomes an important diagnostic and prognostic marker in a number of diseases (primarily oncological). The ability of exosomes to transport biologically active molecules and to protect the cargo from degradation makes them nearly ideal candidates as delivery carriers of RNA in therapeutic or prophylactic regimes. Potential of exosomal surface functionalization enables improved targeting to specific organs, tissues and cells. However, the development of an effective technology for RNA’s loading into exosomes cannot be considered resolved. This review is focused on experimental data on the use of exosomes as vehicles for the delivery of therapeutic and prophylactic RNAs. We briefly consider the biogenesis and functions of exosomes, focusing on those biological properties that make them formidable candidates in the race to develop effective delivery carriers. Furthermore, we describe various techniques of cargo loading into exosomes. Prospects of exosomes application as therapeutic delivery system for siRNAs, miRNAs, and long RNAs are considered.

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Section: Biogenesis Release and Uptake Of Exosomesmentioning

confidence: 99%

Exosomes as Natural Nanocarriers for RNA-Based Therapy and Prophylaxis

et al. 2022

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“…LLPS is a long-studied physicochemical process whose enormous impact in protein biochemistry and cell biology has been recognized recently [17,95]. During the last decades, major cellular membraneless compartments covering a wide range of functions have been discovered [95][96][97][98].…”

Section: Hsp70 and Hsp90 Play Crucial Roles In Disease-related Llpsmentioning

confidence: 99%

“…During the last decades, major cellular membraneless compartments covering a wide range of functions have been discovered [95][96][97][98]. These highly dynamic species are formed by the biomolecular coacervation of usually proteins and RNA to typically keep them dormant during stressful conditions [17], and the molecules within the condensate can be exchanged from the condensed to the dispersed phases. Proteinaceous LLPS is governed by weak, transient, and reversible interactions [99], and a pattern of "stickers" (aromatic residues) and "spacers" (polar moieties) on proteins has been established to determine the phase behavior [100,101].…”

Section: Hsp70 and Hsp90 Play Crucial Roles In Disease-related Llpsmentioning

confidence: 99%

“…Recent breakthroughs in the role of membraneless organelles formed by protein liquid-liquid phase separation (LLPS) in disease progression have brought dynamic condensates into the forefront [14][15][16]. Despite the abundant physiological roles of protein condensates [17], misfolded proteins [16] and pathogenic mutations [14] trigger the assembly into aberrant condensates related to toxicity, which are prevented by chaperone action [16]. In view of the critical role of molecular chaperones preventing aberrant LLPS and/or amyloid aggregation in diseases, understanding the fundamentals of chaperone recognition mechanisms is of utmost relevance for a mechanistic conception of protein misfolding diseases.…”

Section: Introductionmentioning

confidence: 99%

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Mechanistic Insights into the Role of Molecular Chaperones in Protein Misfolding Diseases: From Molecular Recognition to Amyloid Disassembly

Hervás

Oroz

2020

IJMS

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Age-dependent alterations in the proteostasis network are crucial in the progress of prevalent neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, or amyotrophic lateral sclerosis, which are characterized by the presence of insoluble protein deposits in degenerating neurons. Because molecular chaperones deter misfolded protein aggregation, regulate functional phase separation, and even dissolve noxious aggregates, they are considered major sentinels impeding the molecular processes that lead to cell damage in the course of these diseases. Indeed, members of the chaperome, such as molecular chaperones and co-chaperones, are increasingly recognized as therapeutic targets for the development of treatments against degenerative proteinopathies. Chaperones must recognize diverse toxic clients of different orders (soluble proteins, biomolecular condensates, organized protein aggregates). It is therefore critical to understand the basis of the selective chaperone recognition to discern the mechanisms of action of chaperones in protein conformational diseases. This review aimed to define the selective interplay between chaperones and toxic client proteins and the basis for the protective role of these interactions. The presence and availability of chaperone recognition motifs in soluble proteins and in insoluble aggregates, both functional and pathogenic, are discussed. Finally, the formation of aberrant (pro-toxic) chaperone complexes will also be disclosed.

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