Diverse long RNAs are differentially sorted into extracellular vesicles secreted by colorectal cancer cells

exosomes

The regulation and functional roles of secreted coding and long noncoding RNAs (lncRNAs; >200 nt) are largely unknown. Researchers from the Vanderbilt University Medical Center previously showed that mutant KRAS colorectal cancer (CRC) cells release extracellular vesicles (EVs) containing distinct proteomes, microRNAs (miRNAs), and circular RNAs. Here, they comprehensively identify diverse classes of CRC extracellular long RNAs secreted in EVs and demonstrate differential export of specific RNAs. Distinct noncoding RNAs, including antisense transcripts and transcripts derived from pseudogenes, are enriched in EVs compared to cellular profiles. They detected strong enrichment of Rab13 in mutant KRAS EVs and demonstrate functional delivery of Rab13 mRNA to recipient cells. To assay functional transfer of lncRNAs, the researchers implemented a CRISPR/Cas9-based RNA-tracking system to monitor delivery to recipient cells. They show that gRNAs containing export signals from secreted RNAs can be transferred from donor to recipient cells. These data support the existence of cellular mechanisms to selectively export diverse classes of RNA.

Hinger SA, Cha DJ, Franklin JL, Higginbotham JN, Dou Y, Ping J, Shu L, Prasad N, Levy S, Zhang B, Liu Q, Weaver AM, Coffey RJ, Patton JG. (2018) Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells. Cell Rep 25(3):715-725.e4. [article]

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