Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment

Nechooshtan, G., Yunusov, D., Chang, K., Gingeras, T. R. (August 2020) Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment. Nucleic Acids Res, 48 (14). pp. 8035-8049. ISSN 0305-1048 (Print)0305-1048

URL: https://pubmed.ncbi.nlm.nih.gov/32609822/
DOI: 10.1093/nar/gkaa526

Abstract

Extracellular RNAs participate in intercellular communication, and are being studied as promising minimally invasive diagnostic markers. Several studies in recent years showed that tRNA halves and distinct Y RNA fragments are abundant in the extracellular space, including in biofluids. While their regulatory and diagnostic potential has gained a substantial amount of attention, the biogenesis of these extracellular RNA fragments remains largely unexplored. Here, we demonstrate that these fragments are produced by RNase 1, a highly active secreted nuclease. We use RNA sequencing to investigate the effect of a null mutation of RNase 1 on the levels of tRNA halves and Y RNA fragments in the extracellular environment of cultured human cells. We complement and extend our RNA sequencing results with northern blots, showing that tRNAs and Y RNAs in the non-vesicular extracellular compartment are released from cells as full-length precursors and are subsequently cleaved to distinct fragments. In support of these results, formation of tRNA halves is recapitulated by recombinant human RNase 1 in our in vitro assay. These findings assign a novel function for RNase 1, and position it as a strong candidate for generation of tRNA halves and Y RNA fragments in biofluids.

Item Type: Paper
Additional Information: ]
CSHL Authors:
Communities: CSHL labs > Gingeras lab
CSHL Cancer Center Program > Cancer Genetics and Genomics Program
Depositing User: Matthew Dunn
Date: 20 August 2020
Date Deposited: 30 Nov 2020 17:04
Last Modified: 07 Jun 2021 19:23
PMCID: PMC7430647
Related URLs:
URI: https://repository.cshl.edu/id/eprint/39764

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