Publication Date

5-10-2023

Journal

Cell Genomics

DOI

10.1016/j.xgen.2023.100303

PMID

37228754

PMCID

PMC10203258

PubMedCentral® Posted Date

4-20-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

cell-free RNAs, RNA binding proteins, eCLIP, human biofluids, RNA footprint correlation, liquid biopsies, public resource, exRNA carriers, cell-free biomarkers, NIH ERCC

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.

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