Extracellular vesicles carry transcriptional ‘dark matter’ revealing tissue‐specific information

Autor: Navneet Dogra, Tzu‐Yi Chen, Edgar Gonzalez‐Kozlova, Rebecca Miceli, Carlos Cordon‐Cardo, Ashutosh K. Tewari, Bojan Losic, Gustavo Stolovitzky
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Extracellular Vesicles, Vol 13, Iss 8, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2001-3078
DOI: 10.1002/jev2.12481
Popis: Abstract From eukaryotes to prokaryotes, all cells secrete extracellular vesicles (EVs) as part of their regular homeostasis, intercellular communication, and cargo disposal. Accumulating evidence suggests that small EVs carry functional small RNAs, potentially serving as extracellular messengers and liquid‐biopsy markers. Yet, the complete transcriptomic landscape of EV‐associated small RNAs during disease progression is poorly delineated due to critical limitations including the protocols used for sequencing, suboptimal alignment of short reads (20–50 nt), and uncharacterized genome annotations—often denoted as the ‘dark matter’ of the genome. In this study, we investigate the EV‐associated small unannotated RNAs that arise from endogenous genes and are part of the genomic ‘dark matter’, which may play a key emerging role in regulating gene expression and translational mechanisms. To address this, we created a distinct small RNAseq dataset from human prostate cancer & benign tissues, and EVs derived from blood (pre‐ & post‐prostatectomy), urine, and human prostate carcinoma epithelial cell line. We then developed an unsupervised data‐based bioinformatic pipeline that recognizes biologically relevant transcriptional signals irrespective of their genomic annotation. Using this approach, we discovered distinct EV‐RNA expression patterns emerging from the un‐annotated genomic regions (UGRs) of the transcriptomes associated with tissue‐specific phenotypes. We have named these novel EV‐associated small RNAs as ‘EV‐UGRsʼ or “EV‐dark matter”. Here, we demonstrate that EV‐UGR gene expressions are downregulated by ∼100 fold (FDR
Databáze: Directory of Open Access Journals
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