Prions and Prion-like assemblies in neurodegeneration and immunity: The emergence of universal mechanisms across health and disease

O’Carroll, Ailís; Coyle, Joanne; Gambin, Yann

doi:10.1016/j.semcdb.2019.11.012

Cited by 25 publications

(23 citation statements)

References 179 publications

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“…Prions are emerging as one of the most fascinating areas of research in plants, but they have long been documented in animals for a variety of bene cial and detrimental functions; serving as structural modules, components of bio lms, binding to RNA binding and exhibiting enzymatic activity etc [26][27][28][29]. Their role in memory responses is also widely reported, being causative agents of neurodegenerative diseases associated with memory loss [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Prion-like proteins reveal crosstalk between Stress and Memory pathways in Plants

Garai¹,

Citu²,

Singla-Pareek³

et al. 2021

Preprint

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Background: Prions can be considered as molecular memory devices, generating reproducible memory of a conformational change. Prion-like proteins (PrLPs) have been widely demonstrated to be present in plants, but their role in plant stress and memory remains unexplored. Results: In this work, we report the widespread presence of PrLPs in plants through a comprehensive analysis of 39 genomes representing major taxonomic groups. We find diverse functional roles associated with these proteins in various species, and we term the entire PrLP complement of a genome, as it’s Prionome . Investigation of rice transcriptomic datasets further delineated the role of PrLPs in stress and developmental responses, leading us to explore whether and to what extent PrLPs may build stress memory. We found the rice prionome to be significantly enriched for Transposons/Retrotransposons (Ts/RTRs), and superimposed it with the corresponding interactome and diurnal transcriptome. Regulatory inferences derived from clustering and overlaying of these datasets revealed a complex network and crosstalk between PrLPs, transcription factors and genes known to be involved in stress priming. Conclusion: This work connects transient and trans-generational memory mechanisms in plants with prion-like proteins, suggesting that plant memory may rely upon protein-based signals in addition to chromatin-based epigenetic signals. We derive transcriptional regulatory inferences from the rice diurnal gene expression data to identify specific prion-like genes that may be memory hubs in rice. Taken together, our work provides important insights into the anticipated role of prions in stress and memory, paving the way for more focussed studies for validating role of identified PrLPs in memory acclimation.

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Section: Discussionmentioning

confidence: 99%

Prion-like proteins reveal crosstalk between Stress and Memory pathways in Plants

Garai¹,

Citu²,

Singla-Pareek³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Prions are emerging as one of the most fascinating areas of research in plants, but they have long been documented in animals for a variety of beneficial and detrimental functions; serving as structural modules, components of biofilms, binding to RNA binding and exhibiting enzymatic activity etc (Blanco et al, 2012;Wickner et al, 2015;Wulf et al, 2017;O'Carroll et al, 2020). Their role in memory responses is also widely reported, being causative agents of neurodegenerative diseases associated with memory loss (Prusiner, 2012;Aguzzi and Lakkaraju, 2016;Scheckel and Aguzzi, 2018).…”

Section: Discussionmentioning

confidence: 99%

Plant Prionome maps reveal specific roles of prion-like proteins in stress and memory

Garai

Citu

Pandey

et al. 2020

Preprint

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Prions can be considered as molecular memory devices, generating reproducible memory of a conformational change. Prion-like proteins (PrLPs) have been demonstrated to be present in plants, but their role in plant stress and memory remains largely unexplored. In this work, we report the widespread presence of PrLPs in plants through a comprehensive analysis of 39 genomes representing major taxonomic groups. We find diverse functional roles associated with plant prionomes. Investigation of the rice transcriptome further delineated the role of PrLPs in stress and developmental responses, leading us to explore whether and to what extent PrLPs may build stress memory. The rice prionome is significantly enriched for Transposons/Retrotransposons (Ts/RTRs), and we derived transcriptional regulatory inferences from diurnal gene expression revealing a complex regulatory network between PrLPs, transcription factors and genes known to be involved in stress priming, as well as transient and trans-generational plant memory. Overall, our data suggest that plant memory mechanisms may rely upon protein-based signals embedded in PrLPs, in addition to chromatin-based epigenetic signals and provides important insights into the anticipated role of prions in stress and memory.

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“…The recent description of prion-like polymerization signalling, not only in diseases but also in non-pathogenic conditions, as an activation mechanism in innate immunity, has opened a new field of research, in which ASC specks play a central role [23]. The formation of functional platforms by prion-like propagation generates faster and stronger responses to danger, which represents an essential attribute of innate defence mechanisms; however, this response needs to be tightly regulated [13].…”

Section: Asc Speck Functionsmentioning

confidence: 99%

Unknown/enigmatic functions of extracellular ASC

2021

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Apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), encoded by PYCARD gene, is a 22 kDa small molecule, which aggregates into ASC specks during inflammasome activation. ASC protein is an adaptor protein present in several inflammasome complexes that performs several intra-and extracellular functions, in monomeric form or as ASC specks, during physiological and pathological processes related to inflammation and adaptive immunity. Extracellular ASC specks (eASC specks) released during cell death by pyroptosis can contribute as a danger signal to the propagation of inflammation via phagocytosis and activation of surrounding cells. ASC specks are found in the circulation of patients with chronic inflammatory diseases and have been considered as relevant blood biomarkers of inflammation. eASC amplifies the inflammatory signal, may induce the production of autoantibodies, transports molecules that bind to this complex, contributing to the generation of antibodies, and can induce the maturation of cytokines promoting the modelling of the adaptive immunity. Although several advances have been registered in the last 21 years, there are numerous unknown or enigmatic gaps in the understanding of the role of eASC specks in the organism. Here, we provide an overview about the ASC protein focusing on the probable roles of eASC specks in several diseases, up to the most recent studies concerning COVID-19.

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Prions and Prion-like assemblies in neurodegeneration and immunity: The emergence of universal mechanisms across health and disease

Cited by 25 publications

References 179 publications

Prion-like proteins reveal crosstalk between Stress and Memory pathways in Plants

Prion-like proteins reveal crosstalk between Stress and Memory pathways in Plants

Plant Prionome maps reveal specific roles of prion-like proteins in stress and memory

Unknown/enigmatic functions of extracellular ASC

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