NCM 2022: Revealing plasma exRNA’s deepest secrets

Due to the rise in transcriptome profiling of liquid biopsies, the RNAome of human blood plasma is slowly but steadily sharing its secrets. The fragmentation status of the extracellular RNA (exRNA) has remained elusive. Due to the unavailability of full-length RNA sequencing data of human plasma, the current hypothesis remains that most, if not all, exRNA in plasma is highly degraded. Although assumed to be generally intact, it currently remains unclear whether intact, circular RNA (circRNAs) circulate in blood plasma. We used nanopore sequencing to obtain full-length exRNA data from low sample input human plasma and its purified EVs. We demonstrated for the first time that human blood plasma does contain full-length mRNA and intact circRNA (e.g., ZC3H6, VAMP3, SMARCA5, etc). Specifically, we show the presence of long RNA transcripts, previously hypothesised to be absent from plasma.