Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains DOI Open Access
Michael J. Strong,

Crystal McLellan,

Brianna Kalpanis

и другие.

Опубликована: Июль 4, 2024

The SARS-CoV-2 nucleocapsid protein (N protein) is critical to viral replication by undergoing liquid-liquid phase separation seed the formation of a ribonucleoprotein (RNP) complex drive genomic RNA (gRNA) translation and in also suppressing both stress granules processing bodies which postulated increase uncoated gRNA availability. N can form biomolecular condensates with broad range host endogenous proteins including binding (RBPs). Amongst these RBPs are that associated pathological neuronal glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, TAR DNA 43 kDa (TDP-43) forms over 95% amyotrophic lateral sclerosis cases. In this study, we demonstrate TDP-43 dependant on C-terminus domain (N-CTD) intrinsically disordered TDP-43. This process markedly accelerated presence RNA. silico modelling suggests condensate formed composed quadriplex C terminus incorporated.

Язык: Английский

The Role of TDP-43 in SARS-CoV-2-Related Neurodegenerative Changes DOI Creative Commons
Dong‐Hwi Kim,

Jae‐Hyeong Kim,

Min‐Tae Jeon

и другие.

Viruses, Год журнала: 2025, Номер 17(5), С. 724 - 724

Опубликована: Май 19, 2025

The coronavirus disease 2019 (COVID-19) pandemic has been linked to long-term neurological effects with multifaceted complications of neurodegenerative diseases. Several studies have found that pathological changes in transactive response DNA-binding protein 43 kDa (TDP-43) are involved these cases. This review explores the causal interactions between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and TDP-43 from multiple perspectives. Some viral proteins SARS-CoV-2 shown induce through its cleavage, aggregation, mislocalization. infection can cause liquid−liquid phase separation stress granule formation, which accelerate condensation TDP-43, resulting host RNA metabolism disruption. proposed interact RNA, though role replication remains be fully elucidated. interaction potentially facilitates replication, while viral-induced oxidative protease activity pathology. Evidence both clinical experimental indicates may contribute sequelae, including amyotrophic lateral sclerosis-like frontotemporal dementia-like features, as well increased phosphorylated deposition central nervous system. Biomarker further support link dysregulation COVID-19 (long COVID). In this review, we presented a novel integrative framework pathology, bridging gap mechanisms neurodegeneration. These findings underscore need for research clarify TDP-43-related neurodegeneration underlying develop therapeutic strategies aimed at mitigating patients long COVID.

Язык: Английский

Процитировано

0
Phase separation of SARS-CoV-2 nucleocapsid protein with TDP-43 is dependant on C-terminus domains DOI Open Access
Michael J. Strong,

Crystal McLellan,

Brianna Kalpanis

и другие.

Опубликована: Июль 4, 2024

The SARS-CoV-2 nucleocapsid protein (N protein) is critical to viral replication by undergoing liquid-liquid phase separation seed the formation of a ribonucleoprotein (RNP) complex drive genomic RNA (gRNA) translation and in also suppressing both stress granules processing bodies which postulated increase uncoated gRNA availability. N can form biomolecular condensates with broad range host endogenous proteins including binding (RBPs). Amongst these RBPs are that associated pathological neuronal glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, TAR DNA 43 kDa (TDP-43) forms over 95% amyotrophic lateral sclerosis cases. In this study, we demonstrate TDP-43 dependant on C-terminus domain (N-CTD) intrinsically disordered TDP-43. This process markedly accelerated presence RNA. silico modelling suggests condensate formed composed quadriplex C terminus incorporated.

Язык: Английский

Процитировано

2