Prions and the concept of polyprionic inheritance

Galkin, A. P.

doi:10.1007/s00294-017-0685-8

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…Recent advances in the development of a methodology of proteomic screening for amyloids allow to move from identifying individual amyloid proteins to systemic analysis of the prevalence and significance of amyloids in different species 9–12 . These methods are based on the resistance of amyloid aggregates to treatment with SDS that makes it possible to separate them from most other non-amyloid protein complexes 13 . The amyloid properties of the proteins identified in such screenings should be confirmed by further individual analysis.…”

Section: Introductionmentioning

confidence: 99%

RNA-binding protein FXR1 is presented in rat brain in amyloid form

Sopova¹,

Koshel²,

Belashova³

et al. 2019

Sci Rep

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Amyloids are β-sheets-rich protein fibrils that cause neurodegenerative and other incurable human diseases affecting millions of people worldwide. However, a number of proteins is functional in the amyloid state in various organisms from bacteria to humans. Using an original proteomic approach, we identified a set of proteins forming amyloid-like aggregates in the brain of young healthy rats. One of them is the FXR1 protein, which is known to regulate memory and emotions. We showed that FXR1 clearly colocalizes in cortical neurons with amyloid-specific dyes Congo-Red, Thioflavines S and T. FXR1 extracted from brain by immunoprecipitation shows yellow-green birefringence after staining with Congo red. This protein forms in brain detergent-resistant amyloid oligomers and insoluble aggregates. RNA molecules that are colocalized with FXR1 in cortical neurons are insensitive to treatment with RNase A. All these data suggest that FXR1 functions in rat brain in amyloid form. The N-terminal amyloid-forming fragment of FXR1 is highly conserved across mammals. We assume that the FXR1 protein may be presented in amyloid form in brain of different species of mammals, including humans.

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Section: Introductionmentioning

confidence: 99%

RNA-binding protein FXR1 is presented in rat brain in amyloid form

Sopova¹,

Koshel²,

Belashova³

et al. 2019

Sci Rep

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“…Amyloid fibrils are often found in the extracellular matrix of bacteria, 114 contributing to biofilm formation. It has even been suggested that this (meta) function of amyloids may have arisen many times independently during the evolution of bacteria 115 . Interestingly, some extracellular proteins were also found to form amyloid fibrils in archaea, 116 adding to the universality of this function.…”

Section: Resultsmentioning

confidence: 99%

“…of bacteria. 115 Interestingly, some extracellular proteins were also found to form amyloid fibrils in archaea, 116 adding to the universality of this function.…”

Section: Overlap Of Cellular Component Go Terms Of Prion Candidates A...mentioning

confidence: 99%

Conserved functions of prion candidates suggest a primeval role of protein self‐templating

et al. 2023

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Amyloid‐based prions have simple structures, a wide phylogenetic distribution, and a plethora of functions in contemporary organisms, suggesting they may be an ancient phenomenon. However, this hypothesis has yet to be addressed with a systematic, computational, and experimental approach. Here we present a framework to help guide future experimental verification of candidate prions with conserved functions to understand their role in the early stages of evolution and potentially in the origins of life. We identified candidate prions in all high‐quality proteomes available in UniProt computationally, assessed their phylogenomic distributions, and analyzed candidate‐prion functional annotations. Of the 27 980 560 proteins scanned, 228 561 were identified as candidate prions (~0.82%). Among these candidates, there were 84 Gene Ontology (GO) terms conserved across the three domains of life. We found that candidate prions with a possible role in adaptation were particularly well‐represented within this group. We discuss unifying features of candidate prions to elucidate the primeval roles of prions and their associated functions. Candidate prions annotated as transcription factors, DNA binding, and kinases are particularly well suited to generating diverse responses to changes in their environment and could allow for adaptation and population expansion into more diverse environments. We hypothesized that a relationship between these functions and candidate prions could be evolutionarily ancient, even if individual prion domains themselves are not evolutionarily conserved. Candidate prions annotated with these universally occurring functions potentially represent the oldest extant prions on Earth and are therefore excellent experimental targets.

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“…Recent advances in the development of a methodology of proteomic screening for amyloids allow to move from identifying individual amyloid proteins to systemic analysis of the prevalence and significance of amyloids in different species (12)(13)(14)(15). These methods are based on the resistance of amyloid aggregates to treatment with SDS that makes it possible to separate them from most other nonamyloid protein complexes (16). The amyloid properties of the proteins identified in such screenings should be confirmed by further individual analysis.…”

Section: Introductionmentioning

confidence: 99%

Amyloid conformers of the FXR1 protein prevent mRNA degradation in cortical neurons

Sopova¹,

Koshel²,

Zadorsky³

et al. 2019

Preprint

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Functional amyloids regulate vital processes in a variety of organisms from bacteria to higher eukaryotes. The development of methods enabling large-scale screening for amyloids opens up opportunity for systemic analysis of the prevalence of amyloids in nature. Using an original proteomic approach, we identified several proteins forming amyloid-like detergent-resistant aggregates in the rat brain. One of them is the FXR1 protein, which is known to regulate memory and emotions (1,2). We demonstrated that in brain FXR1 forms amyloid oligomers and insoluble detergent-resistant aggregates that strongly colocalize with amyloid-specific dye Thioflavin S and bind mRNA molecules. Moreover, we demonstrated that mRNAs colocalized with FXR1 amyloid particles are completely resistant to treatment with RNAse A. Taking into consideration that the members of ribonuclease A superfamily function in neurons (3) we can conclude that amyloid conformers of FXR1 control RNA stability in brain. Thus, in contrast to pathological amyloids that cause neurodegeneration, FXR1 is the functional amyloid in forebrain. We showed that amyloid properties of FXR1 depend on its N-terminal part from 1 to 379 amino acids. This fragment forms amyloid fibrils in vitro that bind Congo red and manifest apple-green birefringence when assayed by polarization microscopy. The amyloid-forming region of FXR1 is highly conserved in mammals. These data suggest that the ability of amyloid conformers of FXR1 to protect mRNAs is characteristic of different mammalian species, including humans. Significance StatementAmyloids are highly ordered cross-β sheet protein fibrils associated with many neurodegenerative diseases including Alzheimer's disease. However, some amyloid proteins regulate vital processes. We identified a set of proteins that form amyloid-like aggregates in the brain of healthy rats. One of them -the FXR1 protein is known to regulate memory and emotions. FXR1 forms amyloid fibrils that bind RNA molecules and prevent their degradation in brain cortex neurons. Amyloid-forming sequence of FXR1 is highly conserved across mammals including human. Discovery of functional amyloids in mammalian brain shows that strategy aimed at the development of universal anti-amyloid drugs is unpromising. Such potential drugs should prevent or suppress formation of pathological aggregates of a certain protein, but not affect functional amyloids.

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Prions and the concept of polyprionic inheritance

Cited by 6 publications

References 34 publications

RNA-binding protein FXR1 is presented in rat brain in amyloid form

RNA-binding protein FXR1 is presented in rat brain in amyloid form

Conserved functions of prion candidates suggest a primeval role of protein self‐templating

Amyloid conformers of the FXR1 protein prevent mRNA degradation in cortical neurons

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