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The Vanderbilt Center for
Extracellular Vesicle Research

exRNA-eCLIP intersection analysis reveals a map of extracellular RNA binding proteins and associated RNAs across major human biofluids and carriers

AUTHORS

LaPlante EL , Stürchler A , Fullem R , Chen D , Starner AC , Esquivel E , Alsop E , Jackson AR , Ghiran I , Pereira G , Rozowsky J , Chang J , Gerstein MB , Alexander RP , Roth ME , Franklin JL , Coffey RJ , Raffai RL , Mansuy IM , Stavrakis S , deMello AJ , Laurent LC , Wang YT , Tsai CF , Liu T , Jones J , Van Keuren-Jensen K , Van Nostrand E , Mateescu B , Milosavljevic A , . Cell genomics. 2023 04 20; 3(5). 100303

ABSTRACT

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.