Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells | Zendy

Scott A. Hinger | Zendy; JeanSébastien Diana | Zendy; Jeffrey L. Franklin | Zendy; James N. Higginbotham | Zendy; Yongchao Dou | Zendy; Jie Ping | Zendy; Lihua Shu | Zendy; Nripesh Prasad | Zendy; Shawn Levy | Zendy; Bing Zhang | Zendy; Qi Liu | Zendy; Alissa M. Weaver | Zendy; Robert J. Coffey | Zendy; James G. Patton | Zendy

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Diverse Long RNAs Are Differentially Sorted into Extracellular Vesicles Secreted by Colorectal Cancer Cells

Author(s) -

Scott A. Hinger,

JeanSébastien Diana,

Jeffrey L. Franklin,

James N. Higginbotham,

Yongchao Dou,

Jie Ping,

Lihua Shu,

Nripesh Prasad,

Shawn Levy,

Bing Zhang,

Qi Liu,

Alissa M. Weaver,

Robert J. Coffey,

James G. Patton

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.09.054

Subject(s) - biology , microrna , microvesicles , long non coding rna , rna , extracellular vesicle , kras , microbiology and biotechnology , non coding rna , exosome , crispr , mutant , meg3 , gene , genetics , mutation

The regulation and functional roles of secreted coding and long noncoding RNAs (lncRNAs; >200 nt) are largely unknown. We previously showed that mutant KRAS colorectal cancer (CRC) cells release extracellular vesicles (EVs) containing distinct proteomes, microRNAs (miRNAs), and circular RNAs. Here, we 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. We 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, we implemented a CRISPR/Cas9-based RNA-tracking system to monitor delivery to recipient cells. We show that gRNAs containing export signals from secreted RNAs can be transferred from donor to recipient cells. Our data support the existence of cellular mechanisms to selectively export diverse classes of RNA.

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