Mammalian RNAi machinery facilitating transcriptional gene silencing (TGS) is the RNA-induced transcriptional gene silencing-like (RITS-like) complex, comprising of Argonaute (Ago) and small interfering RNA (siRNA) components. We have previously demonstrated promoter-targeted siRNA induce TGS in human immunodeficiency virus type-1 (HIV-1) and simian immunodeficiency virus (SIV), which profoundly suppresses retrovirus replication via heterochromatin formation and histone methylation. Here, we examine subcellular co-localization of Ago proteins with promoter-targeted siRNAs during TGS of SIV and HIV-1 infection. Analysis of retrovirus-infected cells revealed Ago1 co-localized with siRNA in the nucleus, while Ago2 co-localized with siRNA in the inner nuclear envelope. Mismatched and scrambled siRNAs were observed in the cytoplasm, indicating sequence specificity. This is the first report directly visualizing nuclear compartment distribution of Ago-associated siRNA and further reveals a novel nuclear trafficking mechanism for RITS-like components involving the actin cytoskeleton. These results establish a model for elucidating mammalian TGS and suggest a fundamental mechanism underlying nuclear delivery of RITS-like components.
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http://dx.doi.org/10.1093/nar/gkr891 | DOI Listing |
J Cell Biol
March 2025
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.
Many cancer cells exhibit increased amounts of paucimannose glycans, which are truncated N-glycan structures rarely found in mammals. Paucimannosidic proteins are proposedly generated within lysosomes and exposed on the cell surface through a yet uncertain mechanism. In this study, we revealed that paucimannosidic proteins are produced by lysosomal glycosidases and secreted via lysosomal exocytosis.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
CNR Institute of Neuroscience, Vedano al Lambro, Italy.
Background: We recently demonstrated that large extracellular vesicles (EVs) released by Aβ-loaded microglia and carrying Aβ (Aβ-EVs) propagate synaptic dysfunction in the mouse brain by moving at the axon surface (Gabrielli et al., Brain, 2022; Falcicchia et al., Brain Commun, 2023).
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Centre for Brain Research, Indian Institute of Science, Bangalore, Karnataka, India.
Background: F-actin plays crucial roles in establishment and maintenance of synapses including post synaptic density organization, facilitation of vesicle trafficking, anchoring of postsynaptic receptors, and involvement in translational machinery. Proteomic analysis of actin-interacting proteins revealed the interaction of PSD-95 with actin in synaptosomes from brain cortex of APP/PS1 mice. PSD-95 functions as a critical scaffold for the assembly of neurotransmitter receptors at the synapse, playing a pivotal role in regulating synaptic strength and plasticity.
View Article and Find Full Text PDFSoft Matter
January 2025
Institute for X-Ray Physics, University of Göttingen, Friedrich-Hund-Platz 1, 37077 Göttingen, Germany.
The eukaryotic cytoskeleton is an intricate network of three types of mechanically distinct biopolymers - actin filaments, microtubules and intermediate filaments (IFs). These filamentous networks determine essential cellular functions and properties. Among them, microtubules are important for intracellular transport and establishing cell polarity during migration.
View Article and Find Full Text PDFAndrology
January 2025
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina-Universidad de Buenos Aires (UBA/CONICET), Buenos Aires, Argentina.
Background: Endocannabinoids like anandamide (AEA), among other lipids, are recognized signaling molecules that participate in reproductive events.
Objectives: Our aims were to characterize orphan G protein-coupled receptor (GPR55) presence; investigate GPR55 activation by AEA and determine GPR55 role in the bovine sperm function.
Materials And Methods: GPR55 presence was assessed by immunocytochemistry.
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