RNA-binding proteins (RBPs) are key regulators of RNA biology, controlling processes ranging from RNA biogenesis to degradation. RBPs interact with regulatory RNAs and assemble into dynamic ribonucleoprotein particles (RNPs) that determine transcript fate. Dysregulation of RBPs is frequently associated with cancer progression, yet the molecular mechanisms underlying RBP-mediated regulation during tumorigenesis remain incompletely understood. A major focus of our research is on stress granules (SGs), dynamic cytoplasmic RNP condensates that form in response to cellular stress and contain specific populations of RNAs and RBPs. SGs are increasingly implicated in cancer development and stress adaptation, but how individual RBPs control RNA recruitment and localization within these condensates remains poorly understood. To characterize RBP-RNA interactions, we developed RNA affinity purification followed by sequencing (RAPseq), a scalable in vitro approach for identifying RNA targets, binding sites and relative binding strength of RBPs. RAPseq and its extensions allow us to investigate RBP binding specificity, the influence of RNA modifications, and cooperative or competitive interactions between RBPs. We are now complementing RAPseq with APEX-seq to investigate RNA localization within stress granules. APEX-seq uses proximity-dependent biotinylation followed by RNA enrichment and high-throughput sequencing to identify RNAs localized in the proximity of specific proteins or subcellular compartments. We are developing an antibody-targeted APEX approach to profile RNAs in proximity to stress-granule RBPs, allowing us to investigate changes in the SG-associated transcriptome under different cellular conditions. The combination of these approaches provides complementary information: RAPseq identifies the intrinsic RNA-binding preferences of SG-associated RBPs, while APEX-seq determines which RNAs are spatially enriched around these proteins in the cellular environment. Integration with RBP perturbation, RNA-seq and functional analyses will allow us to investigate how RBP-RNA interactions regulate stress-granule composition and function, and how these mechanisms are altered in cancer. Understanding the molecular mechanisms controlling RNA recruitment to stress granules may reveal RBP-dependent pathways that contribute to cancer cell adaptation and survival and provide potential targets for future therapeutic strategies.