{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290282/"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290282"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Large-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [RNA-Seq]","description":"Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates transcript isoforms with distinct 3' ends. While several RNA-binding proteins (RBPs) are known to regulate APA, the roles of the vast majority of RBPs in this process remain poorly characterized. Using a large-scale tethered function assay, we screened a library of 879 human RBPs to identify regulators of APA. We discovered 52 RBPs that modulate APA, validated their functions through knockdown PAS-seq and enhanced crosslinking and immunoprecipitation (eCLIP), and developed a fine-tuned transformer model to predict activators of PAS selection. We focused on two unexpected hits: GRB2, an adaptor protein with crucial roles in cell signaling, and RNPS1, a member of the exon junction complex (EJC). We uncovered mechanisms by which they modulate APA using affinity purification mass spectrometry (AP-MS) and biochemical assays. Our screen provides a comprehensive resource of RBPs involved in APA and reveals unexpected roles of signaling factors in APA regulation.","dates":{"publication":"2026/06/29"},"accession":"GSE290282","cross_references":{"GSM":["GSM8809718","GSM8809719","GSM8809758","GSM8809714","GSM8809715","GSM8809759","GSM8809716","GSM8809717","GSM8809790","GSM8809791","GSM8809792","GSM8809793","GSM8809798","GSM8809754","GSM8809755","GSM8809799","GSM8809756","GSM8809757","GSM8809750","GSM8809794","GSM8809751","GSM8809795","GSM8809752","GSM8809796","GSM8809797","GSM8809753","GSM8809747","GSM8809748","GSM8809749","GSM8809780","GSM8809781","GSM8809782","GSM8809787","GSM8809743","GSM8809744","GSM8809788","GSM8809789","GSM8809745","GSM8809746","GSM8809783","GSM8809784","GSM8809740","GSM8809741","GSM8809785","GSM8809786","GSM8809742","GSM8809736","GSM8809737","GSM8809738","GSM8809739","GSM8809770","GSM8809771","GSM8809732","GSM8809776","GSM8809777","GSM8809733","GSM8809778","GSM8809734","GSM8809735","GSM8809779","GSM8809772","GSM8809773","GSM8809774","GSM8809730","GSM8809775","GSM8809731","GSM8809729","GSM8809725","GSM8809769","GSM8809802","GSM8809803","GSM8809726","GSM8809804","GSM8809727","GSM8809728","GSM8809805","GSM8809760","GSM8809721","GSM8809765","GSM8809766","GSM8809722","GSM8809767","GSM8809723","GSM8809800","GSM8809801","GSM8809724","GSM8809768","GSM8809761","GSM8809762","GSM8809763","GSM8809764","GSM8809720"],"GPL":["24676"],"GSE":["290282"],"taxon":["Homo sapiens"],"PMID":["[42361791]"]}}