LncRNA-encoded microproteins: A new form of cargo in cell culture-derived and circulating extracellular vesicles

Advancements in omics-based technologies over the past few years have led to the discovery of numerous biologically relevant peptides encoded by small open reading frames (smORFs) embedded in long noncoding RNA (lncRNA) transcripts (referred to as microproteins here) in a variety of species. However, the mechanisms and modes of action that underlie the roles of microproteins have yet to be fully characterized. Herein, we provide the first experimental evidence of abundant microproteins in extracellular vesicles (EVs) derived from glioma cancer cells, indicating that the EV-mediated transfer of microproteins may represent a novelmechanism for intercellular communication. Intriguingly, when examining human plasma, 48, 11 and 3microproteins were identified from purified EVs, whole plasma and EV-free plasma, respectively, suggesting that circulating microproteins are primarily enriched in EVs. Most importantly, the preliminary data showed that the expression profile of EV microproteins in glioma patient diverged from the health donors, suggesting that the circulating microproteins in EVs might have potential diagnostic application in identifying patients with glioma.

Automated summary

Advancements in omics-based technologies have revealed the abundant presence of microproteins in extracellular vesicles (EVs) derived from glioma cancer cells, suggesting a novel mechanism for intercellular communication. Circulating microproteins are primarily enriched in EVs in human plasma, with preliminary data indicating potential diagnostic applications in identifying glioma patients based on divergent expression profiles of EV microproteins compared to healthy donors.