GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290281/primary200OKOtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290281GEOGSEfalseLarge-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selection [eCLIP]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.2026/06/29GSE290281GSM8809691GSM8809692GSM8809693GSM8809694GSM8809690GSM8809699GSM8809710GSM8809711GSM8809678GSM8809679GSM8809712GSM8809713GSM8809695GSM8809696GSM8809697GSM8809698GSM8809707GSM8809708GSM8809709GSM8809703GSM8809704GSM8809705GSM8809706GSM8809680GSM8809681GSM8809682GSM8809683GSM8809688GSM8809700GSM8809689GSM8809701GSM8809702GSM8809684GSM8809685GSM8809686GSM880968724676290281Homo sapiens[42361791]