Transfer RNAs (tRNAs) are central players in protein synthesis, which in Eukarya need to be delivered from the nucleus to the cytoplasm by specific transport receptors, most of which belong to the evolutionarily conserved beta-importin family. Based on the available literature, we identified two candidates, Xpo-t and Xpo-5 for tRNA export in Trypanosoma brucei. However, down-regulation of expression of these genes did not disrupt the export of tRNAs to the cytoplasm. In search of alternative pathways, we tested the mRNA export complex Mex67-Mtr2, for a role in tRNA nuclear export, as described previously in yeast. Down-regulation of either exporter affected the subcellular distribution of tRNAs. However, contrary to yeast, TbMex67 and TbMtr2 accumulated different subsets of tRNAs in the nucleus. While TbMtr2 perturbed the export of all the tRNAs tested, silencing of TbMex67, led to the nuclear accumulation of tRNAs that are typically modified with queuosine. In turn, inhibition of tRNA nuclear export also affected the levels of queuosine modification in tRNAs. Taken together, the results presented demonstrate the dynamic nature of tRNA trafficking in T. brucei and its potential impact not only on the availability of tRNAs for protein synthesis but also on their modification status.
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http://dx.doi.org/10.1093/nar/gkz671 | DOI Listing |
Virology
January 2025
School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, United Kingdom. Electronic address:
This mini-review examines the strategy of combining viral protein sequence conservation with drug-binding potential to identify novel antiviral targets, focusing on internal proteins of influenza A and other RNA viruses. The importance of combating viral genetic variability and reducing the likelihood of resistance development is emphasised in the context of sequence redundancy in viral datasets. It covers recent structural and functional updates, as well as drug targeting efforts for three internal influenza A viral proteins: Basic Polymerase 2, Nuclear Export Protein, and Nucleoprotein.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, 30602, USA.
In mammalian oocytes, large-scale chromatin organization regulates transcription, nuclear architecture, and maintenance of chromosome stability in preparation for meiosis onset. Pre-ovulatory oocytes with distinct chromatin configurations exhibit profound differences in metabolic and transcriptional profiles that ultimately determine meiotic competence and developmental potential. Here, we developed a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live mouse oocytes.
View Article and Find Full Text PDFStem Cell Res Ther
January 2025
College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, 230032, China.
Background: The aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims to elucidate how NEAT1 regulates mitotic proteins during BMSCs aging.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Hepatology, Center for Pathogen Biology and Infectious Diseases, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, China.
The intricate link between cholesterol metabolism and host immune responses is well recognized, but the specific mechanisms by which cholesterol biosynthesis influences hepatitis B virus (HBV) replication remain unclear. In this study, we show that SREBP2, a key regulator of cholesterol metabolism, inhibits HBV replication by interacting directly with the HBx protein, thereby preventing its nuclear translocation. We also found that inhibiting the ER-to-Golgi transport of the SCAP-SREBP2 complex or blocking SREBP2 maturation significantly enhances HBV suppression.
View Article and Find Full Text PDFIndian J Nephrol
July 2024
Department of Nephrology, Asian Institute of Nephrology and Urology, Dilsukhnagar Hyderabad, India.
Multiple myeloma (MM) represents a difficult-to-treat plasma cell malignancy and the second most common hematologic malignancy in adults, significantly impacting kidney function. The spectrum of kidney involvement in MM is broad, encompassing electrolyte imbalances, tubular injury, and even rare glomerular diseases. The evolution of MM treatment modalities has led to notable improvements in the long-term survival of patients experiencing kidney-related complications.
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