The nuclear double-stranded RNA can be exported to the cytoplasm leading to the incorporation alternative aminoacids into the translated protein, can be retained to the nucleus playing a role on quality control nuclear function or can engaged by vigilin complex initiating the heterochromatin function. In the nucleus this RNA is associated to the protein, a small amount of DNA, sphingomyelin, phosphatidylcholine, and enzymes related to sphingomyelin metabolism such as sphingomyelinase and sphingomyelin-synthase constituting an intranuclear complex. Our data show an association between cholesterol and sphingomyelin that could play a role in double strand formation after RNA synthesis since [3H]-uridine incorporation demonstrates that nuclear double stranded RNA is new-synthesized. The presence of the lamin B as a protein of the intranuclear complex suggests that it could correspond to the transcription sites associated to the inner nuclear membrane.
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http://dx.doi.org/10.1016/j.abb.2006.11.020 | DOI Listing |
bioRxiv
December 2024
Human Biology Division, Fred Hutchinson Cancer Center, Seattle, WA 98109.
RNA-driven protein aggregation leads to cellular dysregulation by sequestering regulatory proteins, disrupting normal cellular processes, and contributing to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar-associated RNA and human satellite II (HSATII) repeat RNA. Stable intranuclear RNAs drive protein aggregation in DUX4-expressing muscle cells.
View Article and Find Full Text PDFClin Neurophysiol
December 2024
Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Objective: Neuronal Intranuclear Inclusion Disease (NIID) is a neurodegenerative disease affecting the central and peripheral nerves. We aimed to assess the pathophysiological features of peripheral nerve dysfunction in NIID.
Methods: We observed six unrelated NIID patients through clinical records, nerve conduction studies, and multiple measures of motor nerve excitability.
Biochem Biophys Res Commun
January 2025
Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan; Course of Biological Science, Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan. Electronic address:
Intranuclear protein quality control (PQC) is critical for protein homeostasis (or proteostasis) in non-dividing cells including brain nerve cells, but its molecular mechanism remains unresolved. In nutrient-starved conditions, elimination of nucleolar proteins is critical for cell viability in budding yeast, providing a model system to study the mechanisms involved in intranuclear PQC. The nuclear-specific endosomal sorting complex required for transport (ESCRT) CHMP7/Chm7 is linked to neurodegenerative diseases, but its known role is limited.
View Article and Find Full Text PDFJ Chem Phys
December 2024
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA.
We theoretically investigate how the intranuclear environment influences the charge of a nucleosome core particle (NCP)-the fundamental unit of chromatin consisting of DNA wrapped around a core of histone proteins. The molecular-based theory explicitly considers the size, shape, conformation, charge, and chemical state of all molecular species-thereby linking the structural state with the chemical/charged state of the system. We investigate how variations in monovalent and divalent salt concentrations, as well as pH, affect the charge distribution across different regions of an NCP and quantify the impact of charge regulation.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.
We theoretically investigate how the intranuclear environment influences the charge of a nucleosome core particle (NCP) - the fundamental unit of chromatin consisting of DNA wrapped around a core of histone proteins. The molecular-based theory explicitly considers the size, shape, conformations, charges, and chemical states of all molecular species - thereby linking the structural state with the chemical/charged state of the system. We investigate how variations in monovalent and divalent salt concentrations, as well as pH, affect the charge distribution across different regions of an NCP and quantify the impact of charge regulation.
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