CircRNA_0000927 promotes inflammatory response to neuronal injury via miR-126a-5p/PGC-1α axis in acute ischemic stroke DOI Creative Commons
Meng Wang, Hong Li,

Yulin Qian

et al.

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 1, 2022

Abstract Purpose We investigated the role of CircRNA_0000927 on occurrence and development acute ischemic stroke (AIS) neuronal injury by targeting miR-126a-5p/PGC-1α axis to find a novel clinical drug target prediction treatment AIS. Methods The mouse AIS animal model was used in vivo experiments hypoxia/reoxygenation cell vitro established. Firstly, infarction volume pathological changes hippocampal neurons were detected using HE staining. Secondly, rat primary neuron apoptosis flow cytometry assay. numbers neuron, microglia astrocytes immunofluorescence (IF). Furthermore, binding detection performed bioinformatics database double luciferase reporter localization fluorescence situ hybridization (FISH). CircRNA_0000927, miR-126a-5p PGC-1α mRNA expression RT-qPCR. NLRP3, ASC, Caspase-1 protein Western blotting. IL-1β ELISA Results Mouse four-vessel occlusion could easily establish model, had an obvious time-dependence. staining showed that, compared with sham group, deteriorated group. significantly reduced, while activated. Moreover, confirmed site circRNA_0000927 PGC-1α. down-regulated up-regulated . At same time, inflammasome pro-inflammatory factor vitro. over-expression inhibitor inhibit up-regulate Finally, transfected significant relieving injury. Conclusion promotes inflammatory response via

Language: Английский

RNA granules in neuronal plasticity and disease DOI Open Access

Karl E. Bauer,

Bruna R. de Queiroz, Michael Kiebler

et al.

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(7), P. 525 - 538

Published: May 16, 2023

Language: Английский

Citations

29
The mammalian midbody and midbody remnant are assembly sites for RNA and localized translation DOI Creative Commons
Sung Jin Park, Randall D. Dahn, Elif Kurt

et al.

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(19), P. 1917 - 1932.e6

Published: Aug. 7, 2023

Long ignored as a vestigial remnant of cytokinesis, the mammalian midbody (MB) is released post-abscission inside large extracellular vesicles called MB remnants (MBRs). Recent evidence suggests that MBRs can modulate cell proliferation and fate decisions. Here, we demonstrate matrix site ribonucleoprotein assembly enriched in mRNAs encode proteins involved fate, oncogenesis, pluripotency, which are calling granule. Both MBs sites spatiotemporally regulated translation, initiated when nascent daughter cells re-enter G1 continues after release. MKLP1 ARC necessary for localization translation RNA dark zone, whereas ESCRT-III to maintain levels MB. Our work reveals unique event occurs during abscission within vesicle.

Language: Английский

Citations

26
Ribosome inactivation regulates translation elongation in neurons DOI Creative Commons
Bastian Popper,

Martina Bürkle,

Giuliana Ciccopiedi

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(2), P. 105648 - 105648

Published: Jan. 15, 2024

Cellular plasticity is crucial for adapting to ever-changing stimuli. As a result, cells consistently reshape their translatome, and, consequently, proteome. The control of translational activity has been thoroughly examined at the stage translation initiation. However, regulation ribosome speed in widely unknown. In this study, we utilized timed runoff approach along with proteomics and transmission electron microscopy, investigate global kinetics cells. We found that speeds vary amongst various cell types, such as astrocytes, induced pluripotent human stem cells, neural rat neurons. Of all types studied, mature cortical neurons exhibit highest rate translation. This finding particularly remarkable because express eEF2 lower levels than other types. Neurons solve conundrum by inactivating fraction ribosomes. increase leads reduction inactive ribosomes an enhancement active ones. Processes alter demand ribosomes, like neuronal excitation, cause increased inactivation redundant eEF2-dependent manner.Our data suggest novel regulatory mechanism which dynamically inactivate facilitate remodelling. These findings have important implications developmental brain disorders characterised by, among things, aberrant

Language: Английский

Citations

8
RNP components condense into repressive RNP granules in the aging brain DOI Creative Commons
Kavya Vinayan Pushpalatha, Mathilde Solyga, Akira Nakamura

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 19, 2022

Cytoplasmic RNP condensates enriched in mRNAs and proteins are found various cell types associated with both buffering regulatory functions. While a clear link has been established between accumulation of aberrant aggregates progression aging-related neurodegenerative diseases, the impact physiological aging on neuronal never explored. Through high-resolution imaging, we uncover that components progressively cluster into large yet dynamic granules Drosophila brain. We further show age-dependent clustering is caused by an increase stoichiometry conserved helicase Me31B/DDX6, requires PKA kinase activity. Finally, our functional analysis reveals mRNA species recruited to upon exhibit translational repression, indicating co-clustering selected translation regulators repressive may contribute specific post-transcriptional changes gene expression observed course aging.

Language: Английский

Citations

21
DEAD/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders DOI

Chiara Fiorenzani,

Adele Mossa,

Silvia De Rubeis

et al.

Trends in Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Current perspectives in drug targeting intrinsically disordered proteins and biomolecular condensates DOI Creative Commons
Caolitao Qin, Yunlong Wang, Jianming Zheng

et al.

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: May 5, 2025

Intrinsically disordered proteins (IDPs) and biomolecular condensates are critical for cellular processes physiological functions. Abnormal can cause diseases such as cancer neurodegenerative disorders. IDPs, including intrinsically regions (IDRs), were previously considered undruggable due to their lack of stable binding pockets. However, recent evidence indicates that targeting them influence processes. This review explores current strategies target IDPs condensates, potential improvements, the challenges opportunities in this evolving field.

Language: Английский

Citations

0
The dependence of basal forebrain cholinergic neurons on NGF: The case in Alzheimer pathology DOI
A. Claudio Cuello, Sonia Do Carmo

Handbook of clinical neurology, Journal Year: 2025, Volume and Issue: unknown, P. 95 - 122

Published: Jan. 1, 2025

Language: Английский

Citations

0
Stress granules: emerging players in neurodegenerative diseases DOI Creative Commons
Lin Yuan,

Lihong Mao,

Yanming Huang

et al.

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: May 12, 2025

Abstract Stress granules (SGs) are membraneless organelles formed in the cellular cytoplasm under stressful conditions through liquid–liquid phase separation (LLPS). SG assembly can be both dependent and independent of eIF2α pathway, whereas protein quality control systems mediate disassembly. Chaperones specific domains RNA-binding proteins strongly contribute to regulation dynamics. Chronic stress, arising association with aging, may promote persistent SGs that difficult disassemble, thereby acting as a potential pathological nidus for aggregation neurodegenerative diseases (NDDs). In this review, we discuss dynamics factors involved We also highlight relationship among LLPS, SGs, pathogenesis different NDDs. More importantly, summarize assembly-disassembly, which double-edged sword pathophysiology This review aims provide new insights into biology pathology

Language: Английский

Citations

0
Pan-cellular organelles and suborganelles—from common functions to cellular diversity? DOI Open Access
Rico Schieweck, Magdalena Götz

Genes & Development, Journal Year: 2024, Volume and Issue: 38(3-4), P. 98 - 114

Published: Feb. 1, 2024

Cell diversification is at the base of increasing multicellular organism complexity in phylogeny achieved during ontogeny. However, there are also functions common to all cells, such as cell division, migration, translation, endocytosis, exocytosis, etc. Here we revisit organelles involved functions, reviewing recent evidence unexpected differences proteins these organelles. For instance, centrosomes or mitochondria differ significantly their protein composition different, sometimes closely related, types. This has relevance for development and disease. Particularly striking high amount diversity RNA-binding other organelles, which brings us review RNA different suborganelles. We include a discussion about (sub)organelles nucleolus ribosomes, type-specific been reported. propose here that heterogeneity compartments represents novel mechanism regulating diversity. One reason can be multiplied by contributions distinct exemplified with moonlighting function. The specialized still perform pan-cellular but mode, discussed centrosomes, mitochondria, vesicles, These serve regulatory hubs storage transport specific functionally important regulators. In this way, they control differentiation, plasticity, survival. further examples highlighting disease examine many more types possible functional relevance.

Language: Английский

Citations

3
Me31B: a key repressor in germline regulation and beyond DOI Open Access
Ming Gao

Bioscience Reports, Journal Year: 2024, Volume and Issue: 44(5)

Published: April 12, 2024

Maternally Expressed at 31B (Me31B), an evolutionarily conserved ATP-dependent RNA helicase, plays important role in the development of germline across diverse animal species. Its cellular functionality has been posited as a translational repressor, participating various metabolism pathways to intricately regulate spatiotemporal expression RNAs. Despite its evident significance, precise and mechanistic underpinnings Me31B remain insufficiently understood. This article endeavors comprehensively review historic recent research on Me31B, distill major findings, discern generalizable patterns Me31B's functions different contexts, provide insights into fundamental mechanism action. The primary focus this centers elucidating Drosophila within germline, while concurrently delving pertinent orthologs other species systems.

Language: Английский

Citations

3