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Maternal circulating syncytiotrophoblast-derived extracellular vesicles contain biologically active 5'-tRNA halves.
Biochem Biophys Res Commun. 2019 10 08; 518(1):107-113.BB

Abstract

The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EV) into the maternal circulation throughout gestation. STB-EV dependent signalling is believed to contribute to the widespread maternal adaptive physiological changes seen in pregnancy. Transfer RNA (tRNA) halves have been identified in vesicles released from other human and murine organ systems, which alter gene expression in target cells. Here, we characterise tRNA-half expression in STB-EV and demonstrate biological activity of a highly abundant tRNA-half. Short RNA from ex-vivo, dual-lobe placental perfusion STB-EV was sequenced, showing that most (>95%) comprised tRNA species. Whole placental tissue contained <50% tRNA species, suggesting selective packaging and export of tRNA into STB-EV. Most tRNA within STB-EV were 5'-tRNA halves cleaved at 30-32 nucleotides. The pattern of tRNA expression differed depending on the size/origin of the STB-EV; this was confirmed by qPCR. Protein synthesis was suppressed in human fibroblasts when they were cultured with a 5'-tRNA half identified from STB-EV sequencing. This study is the first to evaluate tRNA species in STB-EV. The presence of biologically active 5'-tRNA halves, specific to a vesicular origin, suggests a novel mechanism for maternal-fetal signalling in normal pregnancy.

Authors+Show Affiliations

Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK.Nuffield Department of Women's & Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, UK. Electronic address: manu.vatish@wrh.ox.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31405560

Citation

Cooke, William R., et al. "Maternal Circulating Syncytiotrophoblast-derived Extracellular Vesicles Contain Biologically Active 5'-tRNA Halves." Biochemical and Biophysical Research Communications, vol. 518, no. 1, 2019, pp. 107-113.
Cooke WR, Cribbs A, Zhang W, et al. Maternal circulating syncytiotrophoblast-derived extracellular vesicles contain biologically active 5'-tRNA halves. Biochem Biophys Res Commun. 2019;518(1):107-113.
Cooke, W. R., Cribbs, A., Zhang, W., Kandzija, N., Motta-Mejia, C., Dombi, E., Ri, R., Cerdeira, A. S., Redman, C., & Vatish, M. (2019). Maternal circulating syncytiotrophoblast-derived extracellular vesicles contain biologically active 5'-tRNA halves. Biochemical and Biophysical Research Communications, 518(1), 107-113. https://doi.org/10.1016/j.bbrc.2019.08.015
Cooke WR, et al. Maternal Circulating Syncytiotrophoblast-derived Extracellular Vesicles Contain Biologically Active 5'-tRNA Halves. Biochem Biophys Res Commun. 2019 10 8;518(1):107-113. PubMed PMID: 31405560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maternal circulating syncytiotrophoblast-derived extracellular vesicles contain biologically active 5'-tRNA halves. AU - Cooke,William R, AU - Cribbs,Adam, AU - Zhang,Wei, AU - Kandzija,Neva, AU - Motta-Mejia,Carolina, AU - Dombi,Eszter, AU - Ri,Rannya, AU - Cerdeira,Ana Sofia, AU - Redman,Christopher, AU - Vatish,Manu, Y1 - 2019/08/09/ PY - 2019/07/31/received PY - 2019/08/02/revised PY - 2019/08/05/accepted PY - 2019/8/14/pubmed PY - 2020/6/2/medline PY - 2019/8/14/entrez KW - Extracellular vesicles KW - Placenta KW - Pregnancy KW - Signalling KW - tRNA SP - 107 EP - 113 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 518 IS - 1 N2 - The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EV) into the maternal circulation throughout gestation. STB-EV dependent signalling is believed to contribute to the widespread maternal adaptive physiological changes seen in pregnancy. Transfer RNA (tRNA) halves have been identified in vesicles released from other human and murine organ systems, which alter gene expression in target cells. Here, we characterise tRNA-half expression in STB-EV and demonstrate biological activity of a highly abundant tRNA-half. Short RNA from ex-vivo, dual-lobe placental perfusion STB-EV was sequenced, showing that most (>95%) comprised tRNA species. Whole placental tissue contained <50% tRNA species, suggesting selective packaging and export of tRNA into STB-EV. Most tRNA within STB-EV were 5'-tRNA halves cleaved at 30-32 nucleotides. The pattern of tRNA expression differed depending on the size/origin of the STB-EV; this was confirmed by qPCR. Protein synthesis was suppressed in human fibroblasts when they were cultured with a 5'-tRNA half identified from STB-EV sequencing. This study is the first to evaluate tRNA species in STB-EV. The presence of biologically active 5'-tRNA halves, specific to a vesicular origin, suggests a novel mechanism for maternal-fetal signalling in normal pregnancy. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/31405560/Maternal_circulating_syncytiotrophoblast_derived_extracellular_vesicles_contain_biologically_active_5'_tRNA_halves_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(19)31517-7 DB - PRIME DP - Unbound Medicine ER -