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Telomeric repeat-containing RNA (TERRA) constitutes a nucleoprotein component of extracellular inflammatory exosomes.

Publication ,  Journal Article
Wang, Z; Deng, Z; Dahmane, N; Tsai, K; Wang, P; Williams, DR; Kossenkov, AV; Showe, LC; Zhang, R; Huang, Q; Conejo-Garcia, JR; Lieberman, PM
Published in: Proc Natl Acad Sci U S A
November 17, 2015

Telomeric repeat-containing RNA (TERRA) has been identified as a telomere-associated regulator of chromosome end protection. Here, we report that TERRA can also be found in extracellular fractions that stimulate innate immune signaling. We identified extracellular forms of TERRA in mouse tumor and embryonic brain tissue, as well as in human tissue culture cell lines using RNA in situ hybridization. RNA-seq analyses revealed TERRA to be among the most highly represented transcripts in extracellular fractions derived from both normal and cancer patient blood plasma. Cell-free TERRA (cfTERRA) could be isolated from the exosome fractions derived from human lymphoblastoid cell line (LCL) culture media. cfTERRA is a shorter form (∼200 nt) of cellular TERRA and copurifies with CD63- and CD83-positive exosome vesicles that could be visualized by cyro-electron microscopy. These fractions were also enriched for histone proteins that physically associate with TERRA in extracellular ChIP assays. Incubation of cfTERRA-containing exosomes with peripheral blood mononuclear cells stimulated transcription of several inflammatory cytokine genes, including TNFα, IL6, and C-X-C chemokine 10 (CXCL10) Exosomes engineered with elevated TERRA or liposomes with synthetic TERRA further stimulated inflammatory cytokines, suggesting that exosome-associated TERRA augments innate immune signaling. These findings imply a previously unidentified extrinsic function for TERRA and a mechanism of communication between telomeres and innate immune signals in tissue and tumor microenvironments.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 17, 2015

Volume

112

Issue

46

Start / End Page

E6293 / E6300

Location

United States

Related Subject Headings

  • Tetraspanin 30
  • Telomere
  • Signal Transduction
  • RNA, Untranslated
  • Neoplasms
  • Mice
  • Membrane Glycoproteins
  • Inflammation
  • Immunoglobulins
  • Immunity, Innate
 

Citation

APA
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ICMJE
MLA
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Wang, Z., Deng, Z., Dahmane, N., Tsai, K., Wang, P., Williams, D. R., … Lieberman, P. M. (2015). Telomeric repeat-containing RNA (TERRA) constitutes a nucleoprotein component of extracellular inflammatory exosomes. Proc Natl Acad Sci U S A, 112(46), E6293–E6300. https://doi.org/10.1073/pnas.1505962112
Wang, Zhuo, Zhong Deng, Nadia Dahmane, Kevin Tsai, Pu Wang, Dewight R. Williams, Andrew V. Kossenkov, et al. “Telomeric repeat-containing RNA (TERRA) constitutes a nucleoprotein component of extracellular inflammatory exosomes.Proc Natl Acad Sci U S A 112, no. 46 (November 17, 2015): E6293–6300. https://doi.org/10.1073/pnas.1505962112.
Wang Z, Deng Z, Dahmane N, Tsai K, Wang P, Williams DR, et al. Telomeric repeat-containing RNA (TERRA) constitutes a nucleoprotein component of extracellular inflammatory exosomes. Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6293–300.
Wang, Zhuo, et al. “Telomeric repeat-containing RNA (TERRA) constitutes a nucleoprotein component of extracellular inflammatory exosomes.Proc Natl Acad Sci U S A, vol. 112, no. 46, Nov. 2015, pp. E6293–300. Pubmed, doi:10.1073/pnas.1505962112.
Wang Z, Deng Z, Dahmane N, Tsai K, Wang P, Williams DR, Kossenkov AV, Showe LC, Zhang R, Huang Q, Conejo-Garcia JR, Lieberman PM. Telomeric repeat-containing RNA (TERRA) constitutes a nucleoprotein component of extracellular inflammatory exosomes. Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):E6293–E6300.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 17, 2015

Volume

112

Issue

46

Start / End Page

E6293 / E6300

Location

United States

Related Subject Headings

  • Tetraspanin 30
  • Telomere
  • Signal Transduction
  • RNA, Untranslated
  • Neoplasms
  • Mice
  • Membrane Glycoproteins
  • Inflammation
  • Immunoglobulins
  • Immunity, Innate