{"database": "metadata", "table": "run_metadata", "rows": [[10383, "ERR8517249", "ERX8083723", "ERS10517669", "ERP135370", "PRJEB50765", "HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS", "69e2093b-755e-4be3-88b8-5b4a761258fe", "Other", "A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis ALS and frontotemporal dementia FTD. The exact mechanism resulting in these neurodegenerative diseases remains elusive  but RNA toxicity has been implicated as a gain of function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS linked phenotype. We discovered that the RNA binding protein heterogeneous nuclear ribonucleoprotein K HNRNPK can reverse the toxicity of both sense and antisense repeat RNA  which is dependent on its subcellular localization and on RNA recognition  and not on C9 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts  induced pluripotent stem cell iPSC derived motor neurons and postmortem central cortex  suggesting a disrupted HNRNPK function in C9orf72 ALS. In C9 ALS/FTD patient tissue  we discovered an increased nuclear translocation  but reduced expression of Ribonucleotide Reductase Regulatory Subunit M2 RRM2  a downstream target of HNRNPK involved in DNA damage response. Finally  we show that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9 RNA toxicity zebrafish model. Overall  our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9 ALS and demonstrates its link with aberrant DNA damage response  opening novel therapeutic strategies for C9 ALS/FTD.", "ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22", "PUBMED:29302778;PUBMED:35895140", "Modifier control", "hnRNPK 003", "SAMEA12918519", "vib-ku leuven", "ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22|External Id:SAMEA12918519|INSDC center alias:VIB KU Leuven|INSDC center name:vib ku leuven|INSDC first public:2022 08 22T12:15:26Z|INSDC last update:2022 08 22T12:15:26Z|INSDC status:public|Submitter Id:hnRNPK 003|common name:zebrafish|sample name:hnRNPK 003", null, null, null, null, null, null, null, null, "NextSeq 500 paired end sequencing; Raw reads: hnRNPK 003", "webin reads hnRNPK 003", null, "unspecified", null, null, "RNA-Seq", "TRANSCRIPTOMIC", "PolyA", "PAIRED", "ILLUMINA", "NextSeq 500", null, "ERP135370", "Raw reads: hnRNPK 003", "ENA FIRST PUBLIC:2022 08 22|ENA LAST UPDATE:2022 08 22", "hnRNPK_003_R1.fastq.gz hnRNPK_003_R2.fastq.gz", "fastq fastq", 2931486932.0, 19421721.0, "webin reads hnRNPK 003", "0:75.51 1:75.43", "A:759548162;C:700272829;G:700149526;T:770783019;N:733396", 75, 75, null, null, 759548162, 700272829, 700149526, 770783019, 733396, "ERX8083723", "ERS10517669", "ERA8937191", "vib-ku leuven|European Nucleotide Archive", "vib-ku leuven", 2, 0.9621, 0.96378, 0.06994, 0.06876, 0.68757, 0.68998, 0.46746, 0.47041, 76, 75, "B", "B", "biological fallback assumption", "illumina", "nextseq", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "Belgium", "2022-08-22", "Undetermined", "Undetermined", "Undetermined", "Undetermined"]], "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": ["10383"], "units": {}, "query_ms": 9.643211000366136}