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Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment.
Nucleic Acids Res. 2020 Jul 01 [Online ahead of print]NA

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.

Authors+Show Affiliations

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32609822

Citation

Nechooshtan, Gal, et al. "Processing By RNase 1 Forms tRNA Halves and Distinct Y RNA Fragments in the Extracellular Environment." Nucleic Acids Research, 2020.
Nechooshtan G, Yunusov D, Chang K, et al. Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment. Nucleic Acids Res. 2020.
Nechooshtan, G., Yunusov, D., Chang, K., & Gingeras, T. R. (2020). Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa526
Nechooshtan G, et al. Processing By RNase 1 Forms tRNA Halves and Distinct Y RNA Fragments in the Extracellular Environment. Nucleic Acids Res. 2020 Jul 1; PubMed PMID: 32609822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Processing by RNase 1 forms tRNA halves and distinct Y RNA fragments in the extracellular environment. AU - Nechooshtan,Gal, AU - Yunusov,Dinar, AU - Chang,Kenneth, AU - Gingeras,Thomas R, Y1 - 2020/07/01/ PY - 2020/06/26/accepted PY - 2020/06/07/revised PY - 2020/04/19/received PY - 2020/7/2/entrez PY - 2020/7/2/pubmed PY - 2020/7/2/medline JF - Nucleic acids research JO - Nucleic Acids Res. N2 - 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. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/32609822/Processing_by_RNase_1_forms_tRNA_halves_and_distinct_Y_RNA_fragments_in_the_extracellular_environment L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkaa526 DB - PRIME DP - Unbound Medicine ER -
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