GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290248/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290248GEOGSEfalseLarge-scale tethered screen of RNA-binding proteins reveals novel regulators of poly(A) site selectionAlternative 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 screennprovides a comprehensive resource of RBPs involved in APA and reveals unexpected roles of signaling factors in APA regulation.2026/06/29GSE290248GSM8809270GSM8809271GSM8809272GSM8809262GSM8809263GSM8809264GSM8809265GSM8809260GSM8809261GSM8809266GSM8809267GSM8809268GSM8809269GSM8809251GSM8809252GSM8809253GSM8809254GSM8809250GSM8809259GSM8809255GSM8809256GSM8809257GSM8809258GSM8809240GSM8809241GSM8809242GSM8809243GSM8809248GSM8809249GSM8809244GSM8809245GSM8809246GSM8809247GSM8809196GSM8809230GSM8809197GSM8809231GSM8809198GSM8809199GSM8809232GSM8809192GSM8809193GSM8809194GSM8809195GSM8809237GSM8809238GSM8809239GSM8809233GSM8809234GSM8809235GSM8809236GSM8809190GSM8809191GSM8809185GSM8809186GSM8809187GSM8809220GSM8809188GSM8809221GSM8809181GSM8809182GSM8809183GSM8809184GSM8809226GSM8809227GSM8809228GSM8809229GSM8809222GSM8809189GSM8809223GSM8809224GSM8809225GSM8809219GSM8809180GSM8809176GSM8809210GSM8809177GSM8809215GSM8809216GSM8809217GSM8809218GSM8809211GSM8809178GSM8809179GSM8809212GSM8809213GSM8809214GSM8809208GSM8809209GSM8809204GSM8809205GSM8809206GSM8809207GSM8809200GSM8809201GSM8809202GSM880920324676290248Homo sapiens[42361791]