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Epithelial mitochondrial fission-mediated PANoptosis is crucial for ulcerative colitis and its inhibition by saquinavir through Drp1.
Pharmacol Res
December 2024
Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China; Key specialty of Clinical Pharmacy, The first Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510699, China. Electronic address:
Ulcerative colitis (UC) is characterized by increased cell death in intestinal epithelial cell (IEC), which compromises gut barrier function and activates inflammation. Aberrant mitochondrial dynamics have been implicated in various forms of cell death, but it is currently unclear if they play a role in IEC death and colitis pathogenesis. This study aims to investigate the contribution of aberrant mitochondrial dynamics to colitis progression using cellular models, animal models, and clinical samples.
View Article and Find Full Text PDFIdentification of methylation-sensitive human transcription factors using meSMiLE-seq.
bioRxiv
November 2024
Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Transcription factors (TFs) are key players in eukaryotic gene regulation, but the DNA binding specificity of many TFs remains unknown. Here, we assayed 284 mostly poorly characterized, putative human TFs using selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq), revealing 72 new DNA binding motifs. To investigate whether some of the 158 TFs for which we did not find motifs preferably bind epigenetically modified DNA (i.
View Article and Find Full Text PDFDissecting non-B DNA structural motifs in untranslated regions of eukaryotic genomes.
Genomics Inform
November 2024
Department of Biotechnology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, Andhra Pradesh, 522302, India.
The untranslated regions (UTRs) of genes significantly impact various biological processes, including transcription, posttranscriptional control, mRNA stability, localization, and translation efficiency. In functional areas of genomes, non-B DNA structures such as cruciform, curved, triplex, G-quadruplex, and Z-DNA structures are common and have an impact on cellular physiology. Although the role of these structures in cis-regulatory regions such as promoters is well established in eukaryotic genomes, their prevalence within UTRs across different eukaryotic classes has not been extensively documented.
View Article and Find Full Text PDFA comprehensive study of Z-DNA density and its evolutionary implications in birds.
BMC Genomics
November 2024
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Background: Z-DNA, a left-handed helical form of DNA, plays a significant role in genomic stability and gene regulation. Its formation, associated with high GC content and repetitive sequences, is linked to genomic instability, potentially leading to large-scale deletions and contributing to phenotypic diversity and evolutionary adaptation.
Results: In this study, we analyzed the density of Z-DNA-prone motifs of 154 avian genomes using the non-B DNA Motif Search Tool (nBMST).
Suppression of ZBP1-mediated NLRP3 inflammasome by the tegument protein VP22 facilitates pseudorabies virus infection.
mBio
December 2024
Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Article Synopsis
- ZBP1 (Z-DNA binding protein 1) is an immune sensor that activates the NLRP3 inflammasome during viral infections, but this function is inhibited by the herpesvirus pseudorabies virus (PRV) through its VP22 protein.
- The study reveals that VP22 acts as a virulence factor for PRV, preventing ZBP1 from triggering NLRP3 activation, which would normally help combat the infection.
- When ZBP1 is deficient, a recombinant PRV lacking VP22 replicates more effectively, indicating that VP22's interference with ZBP1’s function is crucial for PRV's pathogenicity.
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