{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Camille Stephan-Otto Attolini"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-16346"],"description":["Metabolic dysfunction-associated steatohepatitis (MASH) and its progression to hepatocellular carcinoma remain major clinical challenges. Chronic endoplasmic reticulum (ER) stress, induced by sustained high-fat diet (HFD) intake, promotes hepatic inflammation, lipid accumulation, and hepatocellular dysfunction during MASH pathogenesis. While transcriptional responses are well-characterized, the post-transcriptional mechanisms underlying hepatocyte adaptation to chronic ER stress remain poorly understood. Using an integrative approach combining transcriptomics, ribosome profiling, cytoplasmic polyadenylation analysis, and cis-regulatory mapping, we define the post-transcriptional landscape induced by chronic HFD exposure. To delineate the specific role of chronic ER stress, we use a hepatocyte-specific knockout of a key regulator of translational control under prolonged ER stress. We show that ~70% of HFD-induced gene expression changes are modulated at the translational level. A distinct subset of mRNAs - enriched in suboptimal codons and bearing short poly(A) tails under normal diet - becomes selectively activated upon HFD-induced poly(A) tail elongation. These transcripts, associated with cell cycle, immune response, fibrosis, and tissue remodeling, correlate with MASH severity in both murine models and human samples. Their regulation is mediated by cis-elements in the 3' UTR that coordinate polyadenylation and deadenylation. Loss of this adaptive response exacerbates liver damage and tumor burden in HFD-fed mice."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Sequencing - Libraries were pooled and sequenced with HiSeq 2500.","Sample Treatment - Male C57BL/6J mice were housed under standard conditions. At 6 weeks of age, mice were randomly assigned to either a high-fat diet (HFD) or a normal diet (ND) and fed HFD or ND for 30 weeks when the experiments were perfomed.","Library Construction - RNA libraries were prepared for sequencing using the kit NEBNext® Ultra™ II RNA Library Prep Kit for Illumina® (Cat#E7770), following manufacturer´s instructions and 10-11 cycles of amplification.","Sample Collection - Animals were euthanized and livers were collected. Primary hepatocytes were isolated after tissue dissociation.","Nucleic Acid Extraction - RNA was isolated using TRI-sure reagent (Bioline) according to the manual, using Glycoblue (Ambion) as a carrier."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - Processed data includes raw and rlog normalized counts for each sample.","Sequence Alignment - FastQ files were aligned against the mm10 genome with Bowtie2 STAR 2.5, forcing End-to-End alignment, disabling junction alignments, allowing a 25% of mismatches per read and a minimum of 25 aligned bases. Alignments were sorted and indexed with sambamba v0.5.1. Putative over-amplification artifacts (duplicated reads) were assessed and removed with the same software."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina HiSeq 2500"],"study_type":["RIP-seq"],"species":["Mus musculus"],"pubmed_authors":["Camille Stephan-Otto Attolini"],"additional_accession":[]},"is_claimable":false,"name":"Posttranscriptional reprogramming controls MASLD progression through chronic ER stress adaptation (RIP Seq)","description":"Metabolic dysfunction-associated steatohepatitis (MASH) and its progression to hepatocellular carcinoma remain major clinical challenges. Chronic endoplasmic reticulum (ER) stress, induced by sustained high-fat diet (HFD) intake, promotes hepatic inflammation, lipid accumulation, and hepatocellular dysfunction during MASH pathogenesis. While transcriptional responses are well-characterized, the post-transcriptional mechanisms underlying hepatocyte adaptation to chronic ER stress remain poorly understood. Using an integrative approach combining transcriptomics, ribosome profiling, cytoplasmic polyadenylation analysis, and cis-regulatory mapping, we define the post-transcriptional landscape induced by chronic HFD exposure. To delineate the specific role of chronic ER stress, we use a hepatocyte-specific knockout of a key regulator of translational control under prolonged ER stress. We show that ~70% of HFD-induced gene expression changes are modulated at the translational level. A distinct subset of mRNAs - enriched in suboptimal codons and bearing short poly(A) tails under normal diet - becomes selectively activated upon HFD-induced poly(A) tail elongation. These transcripts, associated with cell cycle, immune response, fibrosis, and tissue remodeling, correlate with MASH severity in both murine models and human samples. Their regulation is mediated by cis-elements in the 3' UTR that coordinate polyadenylation and deadenylation. Loss of this adaptive response exacerbates liver damage and tumor burden in HFD-fed mice.","dates":{"release":"2026-03-05T00:00:00Z","modification":"2026-03-05T10:04:11.442Z","creation":"2025-12-02T11:50:45.68Z"},"accession":"E-MTAB-16346","cross_references":{"ENA":["ERP185952"],"Biostudies":["E-MTAB-16295","E-MTAB-16294","E-MTAB-16293"],"EFO":["EFO_0002944","EFO_0004170","EFO_0005310","EFO_0004917","EFO_0005518","EFO_0003816","EFO_0004184","EFO_0003969"]}}