run_metadata: 33303

This data as json

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
33303	SRR29925301	SRX25419298	SRS22079471	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		pubmed:39541449		Zebrafish gfp 1	GSM8413277		source name:whole organism\|tissue:whole organism\|strain:AB line\|genotype:WT\|geo loc name:missing\|collection date:missing	Zebrafish gfp 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		Samples were homogenized in 200 µl RNAzol® RT Sigma Aldrich in gentleMACS™ M Tubes using gentleMACS™ Octo Dissociator with Heaters Miltenyi Biotec program RNA 02.01. RNA was extracted following the RNAzol® RT extraction protocol. Ribosomal RNA was depleted from 1.0 µg 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.		tissue:whole organism\|strain:AB line\|genotype:WT	GSM8413277	GSM8413277: Zebrafish gfp 1; Danio rerio; RNA Seq	GSM8413277 r1	GSM8413277	1	Samples were homogenized in 200 µl RNAzol® RT Sigma Aldrich in gentleMACS™ M Tubes using gentleMACS™ Octo Dissociator with Heaters Miltenyi Biotec program RNA 02.01. RNA was extracted following the RNAzol® RT extraction protocol. Ribosomal RNA was depleted from 1.0 µg 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.		RNA-Seq	TRANSCRIPTOMIC	cDNA	SINGLE	ILLUMINA	NextSeq 2000		SRP521541			gfp_1_S1_R1_001.fastq.gz	fastq	5995698912.0	53533026.0	GSM8413277 r1	0:112	A:1785573790;C:1251424786;G:1355613253;T:1601762911;N:1324172	112				1785573790	1251424786	1355613253	1601762911	1324172	SRX25419298	SRS22079471	SRA1930695	Institute of Biochemistry II	Institute of Biochemistry II	1	0.64323		0.28918		0.70857		0.46537		112		B		usable mapping rate	illumina	nextseq_v2	unknown	rrna_depletion	lexogen	bulk	unknown	unknown		Unknown	2024-07-23	Undetermined	Undetermined	Whole Organism	All anatomical structures