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acp³U: A Conserved RNA Modification with Lessons Yet to Unfold.
Mol Cell Biol
January 2025
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
RNA modifications are highly conserved across all domains of life, suggesting an early emergence and a fundamental role in cellular processes. The modification 3-(3-amino-3-carboxypropyl)uridine (acp³U) is found in tRNAs of eukaryotes and prokaryotes, and in the 16S rRNA of archaea. In eukaryotic rRNA, a complex modification containing the acp group, macpΨ is present at the analogous position.
View Article and Find Full Text PDFStructure resolved dynamics of type 2M Von Willebrand Disease.
J Thromb Haemost
January 2025
Division of Hematology, Departments of Internal Medicine and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA. Electronic address:
Background: Genetically determined amino acid substitutions in the platelet adhesive A1 domain alter von Willebrand factor's platelet agglutination competence resulting in both gain- (Type 2B) and loss-of-function (Type 2M) phenotypes of Von Willebrand disease. Prior studies of variants in both phenotypes revealed defects in secondary structure that altered stability and folding of the domain. An intriguing observation was that loss of function arose from both misfolding of A1 and, in a few cases, hyper-stabilization of the native structure.
View Article and Find Full Text PDFeIF2α Phosphorylation-ATF4 Axis-Mediated Transcriptional Reprogramming Mitigates Mitochondrial Impairment During ER Stress.
Mol Cells
January 2025
Basic-Clinical Convergence Research Center, School of Biological Sciences, University of Ulsan, Ulsan 44610, Korea. Electronic address:
Eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, which regulates all three unfolded protein response pathways, helps maintain cellular homeostasis and overcome endoplasmic reticulum (ER) stress through transcriptional and translational reprogramming. However, transcriptional regulation of mitochondrial homeostasis by eIF2α phosphorylation during ER stress is not fully understood. Here, we report that the eIF2α phosphorylation-activating transcription factor 4 (ATF4) axis is required for expression of multiple transcription factors (TFs) including nuclear factor erythroid 2-related factor 2 (Nrf2) and their target genes responsible for mitochondrial homeostasis during ER stress.
View Article and Find Full Text PDFExploiting Mitochondria by Triggering a Faulty Unfolded Protein Response Leads to Effective Cardioprotection.
Int J Med Sci
January 2025
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
This study investigates the role of Fundc1 in cardiac protection under high-altitude hypoxic conditions and elucidates its underlying molecular mechanisms. Using cardiomyocyte-specific knockout ( ) mice, we demonstrated that deficiency exacerbates cardiac dysfunction under simulated high-altitude hypoxia, manifesting as impaired systolic and diastolic function. Mechanistically, we identified that Fundc1 regulates cardiac function through the mitochondrial unfolded protein response (mito-UPR) pathway.
View Article and Find Full Text PDFExploring Distinct Second-Order Data Approaches for Thiamine Quantification via Carbon Dot/Silver Nanoparticle FRET Reversion.
Biosensors (Basel)
December 2024
LAQV, REQUIMTE, Department of Chemical Sciences, Laboratory of Applied Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n° 228, 4050-313 Porto, Portugal.
Accurate and selective monitoring of thiamine levels in multivitamin supplements is essential for preventing deficiencies and ensuring product quality. To achieve this, a Förster resonance energy transfer (FRET) system using carbon dots (CDs) as energy donors and citrate-stabilized silver nanoparticles (AgNPs) as energy acceptors was developed. The aqueous synthesis of AgNPs using microwave irradiation was optimized to obtain efficient plasmonic nanoparticles for FRET applications, targeting maximal absorbance intensity, stability, and wavelength alignment.
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