PNNL

Abstract

While the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is now well established, their exRNA cargo and distribution across biofluids is largely unknown. To address this gap, we extend the exRNA Atlas resource by a map of exRNA carried by RBPs (exRBPs). The map was developed through an integrative analysis of ENCODE eCLIP data (150 RBPs) and human exRNA (6,930 samples) in the exRNA Atlas. Computational analysis and experimental validation identify exRBPs in plasma, serum, saliva, urine, and CSF and in cell conditioned media. exRBPs carry exRNA transcripts from small non-coding RNA biotypes including miRNA, piRNA, tRNA, snRNA, snoRNA, and Y RNA, and fragments from protein-coding genes. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and classes of RNPs across human biofluids. Overall we have mapped exRBPs in human biofluids and generated a new map resource for the community.