{"database": "metadata", "table": "run_metadata", "rows": [[33299, "SRR29925296", "SRX25419302", "SRS22079472", "SRP521541", "PRJNA1139080", "Pathogenic Proteotoxicity of Cryptic Splicing is Alleviated by Ubiquitination and ER Phagy", "GSE272836", "Transcriptome Analysis", "RNA splicing and protein degradation systems allow the functional adaptation of the proteome in response to changing cellular contexts. However  the regulatory mechanisms connecting these processes remain poorly understood. Here  we show that impaired spliceosome assembly caused by USP39 deficiency leads to a pathogenic splicing profile characterized by the use of cryptic five prime splice sites. Importantly  disruptive cryptic variants evade mRNA surveillance pathways and are translated into misfolded proteins. These spurious isoforms disrupt proteostasis causing cytosolic protein aggregates and ER stress. Proteotoxic exons activate unfolded protein response  causing CHOP mediated cell death. In response to impaired splicing  eukaryotic cells enhance ubiquitination and ER phagy to alleviate the pathogenic accumulation of proteotoxic isoforms. Our findings show how cryptic splicing induced proteotoxicity can be mitigated  and provide insight into the molecular pathogenesis of spliceosome associated diseases such as retinitis pigmentosa. Overall design: Comparative gene expression profiling analysis of RNA seq data for WT Zebrafish and its morpholino usp39 KD derivarive", null, "pubmed:39541449", null, "Zebrafish  usp39  1", "GSM8413281", null, "source name:whole organism|tissue:whole organism|strain:AB line|genotype:ups39 CRISPR/Cas9 KO|geo loc name:missing|collection date:missing", "Zebrafish  usp39  1", "BCL convert  v4.0.3 Sequence reads were trimmed for adaptor sequences/low quality sequences using Trimmomatic  v0.40 rc1  parameters ILLUMINACLIP: TruSeq3 SE.fa:2:30:10; CROP:111; HEADCROP:12 GENCODE annotation was used to map reads to the zebrafish genome version Danio rerio.GRCz11.110 with STAR  v2.7.11a  parameters:   runMode alignReads:   outSAMtype BAM SortedByCoordinate; Count reads into exons was determined by using the htseq count  v1.99.2 Differential gene expression analysis was done with DESeq2  v1.42.1 Assembly: Danio rerio.GRCz11.110 Supplementary files format and content: tab delminted text file includes raw count for each Sample", "whole organism", null, "Samples were homogenized in 200 \u00b5l RNAzol\u00ae RT Sigma Aldrich in gentleMACS\u2122 M Tubes using gentleMACS\u2122 Octo Dissociator with Heaters Miltenyi Biotec  program RNA 02.01. RNA was extracted following the RNAzol\u00ae RT extraction protocol. Ribosomal RNA was depleted from 1.0 \u00b5g total RNA using RiboCop rRNA Depletion Kit for Human/Mouse/Rat Lexogen following the manufacturer\u2019s instructions. Sequencing libraries were generated using the CORALL RNA Seq kits Lexogen following the manufacturer\u2019s instructions.", null, "tissue:whole organism|strain:AB line|genotype:ups39 CRISPR/Cas9 KO", "GSM8413281", "GSM8413281: Zebrafish  usp39  1; Danio rerio; RNA Seq", "GSM8413281 r1", "GSM8413281", "1", "Samples were homogenized in 200 \u00b5l RNAzol\u00ae RT Sigma Aldrich in gentleMACS\u2122 M Tubes using gentleMACS\u2122 Octo Dissociator with Heaters Miltenyi Biotec  program RNA 02.01. RNA was extracted following the RNAzol\u00ae RT extraction protocol. Ribosomal RNA was depleted from 1.0 \u00b5g total RNA using RiboCop rRNA Depletion Kit for Human/Mouse/Rat Lexogen following the manufacturer's instructions. Sequencing libraries were generated using the CORALL RNA Seq kits Lexogen following the manufacturer's instructions.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "SINGLE", "ILLUMINA", "NextSeq 2000", null, "SRP521541", null, null, "usp39_1_S5_R1_001.fastq.gz", "fastq", 6219261664.0, 55529122.0, "GSM8413281 r1", "0:112", "A:1884475909;C:1283923393;G:1434823696;T:1614670192;N:1368474", 112, null, null, null, 1884475909, 1283923393, 1434823696, 1614670192, 1368474, "SRX25419302", "SRS22079472", "SRA1930695", "Institute of Biochemistry II", "Institute of Biochemistry II", 1, 0.55692, null, 0.23871, null, 0.72368, null, 0.47061, null, 112, null, "B", null, "usable mapping rate", "illumina", "nextseq_v2", "unknown", "rrna_depletion", "lexogen", "bulk", "unknown", "unknown", null, "Unknown", "2024-07-23", "Undetermined", "Undetermined", "Whole Organism", "All anatomical structures"]], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": ["rowid"], "primary_key_values": ["33299"], "units": {}, "query_ms": 8.312514997669496}