GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290282/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290282GEOGSEfalseLarge-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [RNA-Seq]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.2026/06/29GSE290282GSM8809718GSM8809719GSM8809758GSM8809714GSM8809715GSM8809759GSM8809716GSM8809717GSM8809790GSM8809791GSM8809792GSM8809793GSM8809798GSM8809754GSM8809755GSM8809799GSM8809756GSM8809757GSM8809750GSM8809794GSM8809751GSM8809795GSM8809752GSM8809796GSM8809797GSM8809753GSM8809747GSM8809748GSM8809749GSM8809780GSM8809781GSM8809782GSM8809787GSM8809743GSM8809744GSM8809788GSM8809789GSM8809745GSM8809746GSM8809783GSM8809784GSM8809740GSM8809741GSM8809785GSM8809786GSM8809742GSM8809736GSM8809737GSM8809738GSM8809739GSM8809770GSM8809771GSM8809732GSM8809776GSM8809777GSM8809733GSM8809778GSM8809734GSM8809735GSM8809779GSM8809772GSM8809773GSM8809774GSM8809730GSM8809775GSM8809731GSM8809729GSM8809725GSM8809769GSM8809802GSM8809803GSM8809726GSM8809804GSM8809727GSM8809728GSM8809805GSM8809760GSM8809721GSM8809765GSM8809766GSM8809722GSM8809767GSM8809723GSM8809800GSM8809801GSM8809724GSM8809768GSM8809761GSM8809762GSM8809763GSM8809764GSM880972024676290282Homo sapiens[42361791]