RNA regulation in mammalian cells requires complex physical compartmentalisation, using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic dystrophy type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from an expansion of nucleotides CTG (CTGexp) in the DNA encoding DM1 protein kinase (DMPK). The cellular hallmark of DM1 is the formation of nuclear foci that contain expanded DMPK RNA (CUGexp) (with thymine instead of uracil). We report here the deregulation of stress granules (SGs) and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of SGs suggest an altered ability of cells to respond to stress associated with DM1, while changes to the structure and dynamics of SGs and P-bodies suggest that a widespread alteration to the biophysical properties of cellular structures is a consequence of the presence of CUGexp RNA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366894 | PMC |
| http://dx.doi.org/10.1242/dmm.049294 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Emerging of Ultrafine Membraneless Organelles as the Missing Piece of Nanostress: Mechanism of Biogenesis and Implications at Multilevels.
ACS Nano
January 2025
Department of Pharmaceutics, and Nanjing Medical University, Nanjing 211166, P. R. China.
Understanding the interaction between nanomaterials and cellular structures is crucial for nanoparticle applications in biomedicine. We have identified a subtype of stress granules, called nanomaterial-provoked stress granules (NSGs), induced by gold nanorods (AuNRs). These NSGs differ from traditional SGs in their physical properties and biological functions.
View Article and Find Full Text PDFUnderstanding retinal tau pathology through functional 2D and 3D iPSC-derived in vitro retinal models.
Acta Neuropathol Commun
January 2025
Department of Physiology and Pharmacology, Sapienza University of Rome, 00185, Rome, Italy.
The generation of retinal models from human induced pluripotent stem cells holds significant potential for advancing our understanding of retinal development, neurodegeneration, and the in vitro modeling of neurodegenerative disorders. The retina, as an accessible part of the central nervous system, offers a unique window into these processes, making it invaluable for both study and early diagnosis. This study investigates the impact of the Frontotemporal Dementia-linked IVS 10 + 16 MAPT mutation on retinal development and function using 2D and 3D retinal models derived from human induced pluripotent stem cells.
View Article and Find Full Text PDFTDP-43 nuclear retention is antagonized by hypo-phosphorylation of its C-terminus in the cytoplasm.
Commun Biol
January 2025
Université Paris-Saclay, INSERM U1204, Univ Evry, Structure-Activité des Biomolécules Normales et Pathologiques (SABNP), Evry-Courcouronnes, France.
Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), in which TDP-43, a nuclear RNA-binding protein, forms cytoplasmic inclusions. Here, we have developed a robust and automated method to assess protein self-assembly in the cytoplasm using microtubules as nanoplatforms. Importantly, we have analyzed specifically the self-assembly of full-length TDP-43 and its mRNA binding that are regulated by the phosphorylation of its self-adhesive C-terminus, which is the recipient of many pathological mutations.
View Article and Find Full Text PDFDeveloping affordable and efficient heating devices for enhanced live cell imaging in confocal microscopy.
Front Plant Sci
January 2025
Department of Biology, University of Mississippi, University, MS, United States.
Temperature control is crucial for live cell imaging, particularly in studies involving plant responses to high ambient temperatures and thermal stress. This study presents the design, development, and testing of two cost-effective heating devices tailored for confocal microscopy applications: an aluminum heat plate and a wireless mini-heater. The aluminum heat plate, engineered to integrate seamlessly with the standard 160 mm × 110 mm microscope stage, supports temperatures up to 36°C, suitable for studies in the range of non-stressful warm temperatures (e.
View Article and Find Full Text PDFChirality engineering-regulated liquid-liquid phase separation of stress granules and its role in chemo-sensitization and side effect mitigation.
J Colloid Interface Sci
January 2025
Department of Oncology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, PR China. Electronic address:
In recent years, the chiral biological effects of nanomedicines have garnered significant interest. Research has focused on understanding how material chirality affects cellular transcription and metabolism. Stress granules, which are membraneless organelles formed through liquid-liquid phase separation of G3BP1 proteins and related compartments, have been extensively studied and are closely associated with cellular damage repair and metabolism.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!