{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Eugene Berezikov"],"organism":["Nothobranchius furzeri"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-15325"],"description":["The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) regulates cell differentiation, proliferation, and function in various tissues, including the liver, adipose tissue, skin, lung, and hematopoietic system. Studies in rats, mice, humans, and chickens have shown that CEBPA mRNA undergoes alternative translation initiation, producing three C/EBPα protein isoforms. Two of these isoforms act as full-length transcription factors with N-terminal transactivation domains and a C-terminal dimerization and DNA-binding domain. The third isoform is an N-terminally truncated variant, translated from a downstream AUG codon. It competes with full-length isoforms for DNA binding, thereby antagonizing their activity. Expression of the truncated C/EBPα isoform depends on the initial translation of a short upstream open reading frame (uORF) in CEBPA mRNA and subsequent re-initiation at a downstream AUG codon, a process stimulated by mTORC1 signaling. We have generated C/EBPα ΔuORF mutant Nothobranchius furzeri fish and demonstrated that this genetic modification significantly extended both the median and maximal lifespan and improved the healthspan of males. Comparative transcriptome analysis revealed an upregulation of genes and pathways that are associated with healthspan and lifespan regulation in other species."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Library Construction - RNA-seq libraries were prepared according to the Smart-3SEQ protocol (https://doi.org/10.1101/gr.234807.118) using 40 ng of total RNA per sample. The first read starts with 6 nt UMI, followed by a spacer of 0,3 or 6 nt, followed by GGG and the RNA sequence. The second read starts with 6 nt UMI.","Sequencing - Libraries were sequenced on an Illumina NovaSeq X Plus platform.","Sample Collection - Whole fish liver, brain, skin and muscle samples were harvested from three NfCEBPAΔuORF animals and three wild-type animals.","Nucleic Acid Extraction - Total RNA was isolated using TRIzol™ Reagent (Invitrogen) according to the manufacturer’s protocol."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - Raw reads were processed with TrimGalore to remove adapters and polyA-tails and deduplicated using rmdup command from seqkit."],"omics_type":["Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina NovaSeq X"],"pubmed_abstract":["<h4>ABSTRACT</h4>  The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) regulates cell differentiation, proliferation, and function in various tissues, including the liver, adipose tissue, skin, lung, and hematopoietic system. Studies in rats, mice, humans, and chickens have shown that CEBPA mRNA undergoes alternative translation initiation, producing three C/EBPα protein isoforms. Two of these isoforms act as full-length transcription factors with N-terminal transactivation domains and a C-terminal dimerization and DNA-binding domains. The third isoform is an N-terminally truncated variant, translated from a downstream AUG codon. It competes with full-length isoforms for DNA binding, thereby antagonizing their activity. Expression of the truncated C/EBPα isoform depends on the initial translation of a short upstream open reading frame (uORF) in CEBPA mRNA and subsequent re-initiation at a downstream AUG codon, a process stimulated by mTORC1 signaling. We investigated whether the ortholog of the CEBPA gene in the evolutionarily distant, short-lived African turquoise killifish (  Nothobranchius furzeri ) is regulated by similar mechanisms. Our findings reveal that the uORF- mediated regulation of C/EBPα isoform expression is conserved in killifish. Disruption of the uORF selectively eliminates the truncated isoform, leading to unrestrained activity of the full-length C/EBPα isoforms. This genetic modification significantly extended both the median and maximal lifespan and improved the healthspan of male  N. furzeri . These results highlight a conserved mechanism of  CEBPA gene regulation across species and its potential role in modulating the lifespan and aging phenotypes."],"study_type":["RNA-seq of coding RNA"],"species":["Nothobranchius furzeri"],"pubmed_title":["Enhanced C/EBPα function extends healthspan and lifespan in the African turquoise killifish"],"pubmed_authors":["Kirill Ustyantsev","Cornelis Calkhoven","Eugene Berezikov","Christine Müller","Christine Müller, Joscha S. Muck, Gertrud Kortman, Josephine Hartung,  Eugene Berezikov,  Cornelis F. Calkhoven"],"additional_accession":[]},"is_claimable":false,"name":"RNA-seq of different tissues from wild-type and C/EBPα ΔuORF mutant African turquoise killifish Nothobranchius furzeri","description":"The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) regulates cell differentiation, proliferation, and function in various tissues, including the liver, adipose tissue, skin, lung, and hematopoietic system. Studies in rats, mice, humans, and chickens have shown that CEBPA mRNA undergoes alternative translation initiation, producing three C/EBPα protein isoforms. Two of these isoforms act as full-length transcription factors with N-terminal transactivation domains and a C-terminal dimerization and DNA-binding domain. The third isoform is an N-terminally truncated variant, translated from a downstream AUG codon. It competes with full-length isoforms for DNA binding, thereby antagonizing their activity. Expression of the truncated C/EBPα isoform depends on the initial translation of a short upstream open reading frame (uORF) in CEBPA mRNA and subsequent re-initiation at a downstream AUG codon, a process stimulated by mTORC1 signaling. We have generated C/EBPα ΔuORF mutant Nothobranchius furzeri fish and demonstrated that this genetic modification significantly extended both the median and maximal lifespan and improved the healthspan of males. Comparative transcriptome analysis revealed an upregulation of genes and pathways that are associated with healthspan and lifespan regulation in other species.","dates":{"release":"2026-05-26T00:00:00Z","modification":"2026-05-26T11:48:55.607Z","creation":"2025-07-04T13:14:24.218Z"},"accession":"E-MTAB-15325","cross_references":{"ENA":["ERP174666"],"EFO":["EFO_0002944","EFO_0004170","EFO_0005518","EFO_0003816","EFO_0003738","EFO_0004184"],"doi":["10.1101/2025.02.18.638802"]}}