RNA Granules and Their Role in Neurodegenerative Diseases

Sidibé, Hadjara; Velde, Christine Vande

doi:10.1007/978-3-030-31434-7_8

Cited by 19 publications

(14 citation statements)

References 289 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aggregates formed by SETD2 may indicate the formation of functional bodies such as the RNA granules. RNA granules are micron-sized membrane-less entities formed by phase separation [ 36 ]. RNA granules are complex structures that contain ribosomal subunits, translation factors, scaffold, and RNA-binding proteins.…”

Section: Discussionmentioning

confidence: 99%

Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition

Bhattacharya

Workman

2020

Epigenetics & Chromatin

View full text Add to dashboard Cite

Background The histone H3K36me3 mark regulates transcription elongation, pre-mRNA splicing, DNA methylation, and DNA damage repair. However, knowledge of the regulation of the enzyme SETD2, which deposits this functionally important mark, is very limited. Results Here, we show that the poorly characterized N-terminal region of SETD2 plays a determining role in regulating the stability of SETD2. This stretch of 1–1403 amino acids contributes to the robust degradation of SETD2 by the proteasome. Besides, the SETD2 protein is aggregate prone and forms insoluble bodies in nuclei especially upon proteasome inhibition. Removal of the N-terminal segment results in the stabilization of SETD2 and leads to a marked increase in global H3K36me3 which, uncharacteristically, happens in a Pol II-independent manner. Conclusion The functionally uncharacterized N-terminal segment of SETD2 regulates its half-life to maintain the requisite cellular amount of the protein. The absence of SETD2 proteolysis results in a Pol II-independent H3K36me3 deposition and protein aggregation.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition

Bhattacharya

Workman

2020

Epigenetics & Chromatin

View full text Add to dashboard Cite

show abstract

“…Other recent reviews note the importance of PTM in neurodegeneration associated with SGs (Hofweber & Dormann, 2019;N. Kedersha et al, 2013;Mahboubi & Stochaj, 2017;Protter & Parker, 2016;Sidibe & Vande Velde, 2019;Wolozin & Ivanov, 2019).…”

Section: Posttranslational Modifications Of Stress Granule Componenmentioning

confidence: 99%

“…Even though these two stress conditions are often used side by side to provoke SG formation, to the best of our knowledge, differences in the regulation and composition of SGs induced by both stresses have not yet been reviewed. We attempt to present a thorough comparison of heat‐ and arsenite stress‐induced SGs and discuss their possible usefulness as models for the investigation of neurodegenerative disorders, of which RNA granule dysfunction has been suggested as one of the leading causes (Sidibe & Vande Velde, 2019).…”

Section: How Do Cells Profit From the Assembly Of Stress Granules?mentioning

confidence: 99%

“…In these neurodegenerative disorders, defects in SG formation and disassembly are considered to be part of the leading processes that cause pathologies. SG components are thus considered possible therapeutic targets (Aulas & Vande Velde, 2015; Reineke & Neilson, 2019; Sidibe & Vande Velde, 2019; Wolozin & Ivanov, 2019). Neurodegenerative diseases are often characterized by protein inclusions, a subset of which colocalizes with SG markers, for example, the RNA‐binding proteins T‐cell‐restricted intracellular antigen TIA‐1 (TIA‐1), G3BP, and tristetraprolin (TTP).…”

Section: Stress Granules and Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

Changing faces of stress: Impact of heat and arsenite treatment on the composition of stress granules

Frydrýšková¹,

Mašek²,

Pospíšek

2020

WIREs RNA

View full text Add to dashboard Cite

Stress granules (SGs), hallmarks of the cellular adaptation to stress, promote survival, conserve cellular energy, and are fully dissolved upon the cessation of stress treatment. Different stresses can initiate the assembly of SGs, but arsenite and heat are the best studied of these stresses. The composition of SGs and posttranslational modifications of SG proteins differ depending on the type and

show abstract

“…The interplay between genetics and the environment is suspected to play a major role in the development and/or progression of ALS and FTD (Al-Chalabi and Hardiman, 2013). Recent work places stress granules, a core aspect of the integrated stress response that facilitates cellular recovery from adverse environmental exposures, as a critical component of disease pathogenesis (Dewey et al, 2010;Boeynaems et al, 2017;Mackenzie et al, 2017;Sidibé and Vande Velde, 2019). These micron-sized cytoplasmic foci form concomitant with translational arrest following stress exposure and are proposed to protect and/or sort non-translating mRNAs Kedersha, 2006, 2008).…”

Section: Introductionmentioning

confidence: 99%

TDP-43 stabilizes transcripts encoding stress granule protein G3BP1: potential relevance to ALS/FTD

Sidibé

Khalfallah

Xiao

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

TDP-43 nuclear depletion and concurrent cytoplasmic accumulation in vulnerable neurons is a hallmark feature of progressive neurodegenerative proteinopathies such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cellular stress signalling and stress granule dynamics are now recognized to play a role in ALS/FTD pathogenesis. Defective stress granule assembly is associated with increased cellular vulnerability and death. G3BP1 (Ras-GAP SH3-domain-binding protein 1) is a critical stress granule assembly factor. Here, we define that TDP-43 stabilizes G3BP1 transcripts via direct binding of a highly conserved cis regulatory element within the 3’UTR. Moreover, we show in vitro and in vivo that nuclear TDP-43 depletion is sufficient to reduce G3BP1 protein levels. Finally, we establish that G3BP1 transcripts are reduced in ALS/FTD patient neurons bearing TDP-43 cytoplasmic inclusions/nuclear depletion. Thus, our data suggest that, in ALS/FTD, there is a compromised stress granule response in disease-affected neurons due to impaired G3BP1 mRNA stability caused by TDP-43 nuclear depletion. These data implicate TDP-43 and G3BP1 loss of function as contributors to disease.

show abstract

RNA Granules and Their Role in Neurodegenerative Diseases

Cited by 19 publications

References 289 publications

Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition

Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition

Changing faces of stress: Impact of heat and arsenite treatment on the composition of stress granules

TDP-43 stabilizes transcripts encoding stress granule protein G3BP1: potential relevance to ALS/FTD

Contact Info

Product

Resources

About