Although the RNA helicase Upf1 has hitherto been examined mostly in relation to its cytoplasmic role in nonsense mediated mRNA decay (NMD), here we report high-throughput ChIP data indicating genome-wide association of Upf1 with active genes in Schizosaccharomyces pombe. This association is RNase sensitive, correlates with Pol II transcription and mRNA expression levels. Changes in Pol II occupancy were detected in a Upf1 deficient (upf1Δ) strain, prevalently at genes showing a high Upf1 relative to Pol II association in wild-type. Additionally, an increased Ser2 Pol II signal was detected at all highly transcribed genes examined by ChIP-qPCR. Furthermore, upf1Δ cells are hypersensitive to the transcription elongation inhibitor 6-azauracil. A significant proportion of the genes associated with Upf1 in wild-type conditions are also mis-regulated in upf1Δ. These data envisage that by operating on the nascent transcript, Upf1 might influence Pol II phosphorylation and transcription.
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http://dx.doi.org/10.1093/nar/gkab1249 | DOI Listing |
Eur J Med Genet
December 2024
Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan. Electronic address:
Nonsense-mediated mRNA decay represents a biologic clearing system against aberrant mRNAs harboring nonsense and frameshift mutations and depends on three factors, UPF1, UPF2, and UPF3 (UPF3A, UPF3B). While germline pathogenic variants of UPF3B and UPF2 are known to be associated with neurodevelopmental disorders, germline variants in UPF1 have not been reported, until date, as being associated with any human disorders. Herein, we report two unrelated patients with de novo UPF1 variants.
View Article and Find Full Text PDFJ Biol Chem
November 2024
Department of Pathogenic Biology, School of Medicine, Nantong University, Nantong, China; Laboratory of Medical Science, School of Medicine, Nantong University, Nantong, China. Electronic address:
3'UTRs are recognized for their role in regulating mRNA turnover while the turnover of a specific group of mRNAs mediated by coding sequences (CDSs) remains poorly understood. N4BP1 is a critical inflammatory regulator in vivo with a molecular mechanism that is not yet clearly defined. Our study reveals that N4BP1 efficiently degrades its mRNA targets via CDS rather than the 3'-UTR.
View Article and Find Full Text PDFBiochim Biophys Acta Gene Regul Mech
December 2024
University of Strasbourg, UPR CNRS 9002, ARN, IUT Louis Pasteur, Schiltigheim, France. Electronic address:
BCL11b is a transcription regulator and a tumor suppressor involved in lymphomagenesis, central nervous system (CNS) and immune system developments. BCL11b favors persistence of HIV latency and contributes to control cell cycle, differentiation and apoptosis in multiple organisms and cell models. Although BCL11b recruits the non-coding RNA 7SK and epigenetic enzymes to regulate gene expression, BCL11b-associated ribonucleoprotein complexes are unknown.
View Article and Find Full Text PDFMol Med
September 2024
Emergency trauma College of Hainan Medical University, Haikou, 571199, Hainan Province, China.
Background: Macrophage pyroptosis is a pivotal inflammatory mechanism in sepsis-induced lung injury, however, the underlying mechanisms remain inadequately elucidated.
Methods: Lipopolysaccharides (LPS)/adenosine triphosphate (ATP)-stimulated macrophages and cecal ligation and puncture (CLP)-induced mouse model for sepsis were established. The levels of key molecules were examined by qRT-PCR, Western blotting, immunohistochemistry (IHC) and ELISA assay.
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