98%
921
2 minutes
20
Recent advancements in genome analysis technology have revealed the presence of read-through transcripts in which transcription continues by skipping the polyA signal. We here identified and characterized a new read-through transcript, . With cDNA amplification from THP-1 cells, the product was successfully generated. We also generated , another isoform, by introducing point mutations. Notably, while APOE3 and APOE4 exhibited extracellular secretion, both TOMM40-APOE3 and TOMM40-APOE4 were localized exclusively to the mitochondria. But functionally, they did not affect mitochondrial membrane potential. Cell death induction studies illustrated increased cell death with TOMM40-APOE3 and TOMM40-APOE4, and we did not find any difference in cellular function between the two isoforms. These findings indicated that the new mitochondrial protein TOMM40-APOE has cell toxic ability.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10778128 | PMC |
http://dx.doi.org/10.3390/cells13010069 | DOI Listing |
Am J Med Genet A
August 2025
Department of Pediatrics, The Ohio State College of Medicine, Columbus, Ohio, USA.
The nucleosome remodeling and deacetylation (NuRD) complex is a major chromatin regulator and plays a critical role in regulating gene transcription, genome integrity, and cell cycle progression. Heterozygous variants in GATAD2B, a core NuRD component, have been reported to cause GATAD2B-Associated Neurodevelopmental Disorder (GAND), an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, hypotonia, and distinctive craniofacial features. The vast majority of disease-causing variants in GATAD2B reported to date are loss-of-function (nonsense, frameshift, or splice site) variants.
View Article and Find Full Text PDFAdv Exp Med Biol
July 2025
Department of Ophthalmology & Vision Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
The next frontier in genetic therapy for IRDs is the correction or silencing of specific mutations. This is of relevance to conditions with dominant negative and gain-of-function disease mechanisms, or with causative genes that are too large for gene replacement using AAV vectors. We discuss two approaches that have reached the stage of human clinical trials: CRISPR-Cas9 based gene editing and post-transcriptional gene silencing using antisense oligonucleotides.
View Article and Find Full Text PDFNat Commun
July 2025
Department of Pathology & Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Virus genomes harbor compacted repertoires of genes and regulatory elements. Through long-read sequencing, we provide a comprehensive Epstein Barr virus (EBV) transcriptome analysis, identifying 1453 transcript isoforms and resolving the major isoform of all but one lytic reading frame. Further, we categorize each transcript according to their dependence on viral DNA replication.
View Article and Find Full Text PDFCell Death Discov
June 2025
Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
Fanconi anemia (FA) is caused by mutations affecting FANC genes involved in DNA repair, with nearly 20% of FA patients harboring nonsense mutations. Ataluren (PTC124) is a translational read-through-inducing drug (TRID) already approved in Europe that has a well-established safety profile even in pediatric patients. Amlexanox, an anti-inflammatory drug, also promotes read-through of premature stop codons caused by nonsense mutations.
View Article and Find Full Text PDFPLoS One
May 2025
Department of Biology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Eukaryotic life has been shaped fundamentally by the integration of bacterial endosymbionts. The trypanosomatid Angomonas deanei that contains a β-proteobacterial endosymbiont, represents an emerging model to elucidate initial steps in symbiont integration. Although the repertoire of genetic tools for A.
View Article and Find Full Text PDF