Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL

Walsh, N. C., Alexander, K. A., Manning, C. A., Karmakar, S. K., Wang, J. F., Weyand, C. M., Pettit, A. R. and Gravallese, E. M. (2013) Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL. Genes and Immunity, 14 5: 336-345. doi:10.1038/gene.2013.29

Author Walsh, N. C.
Alexander, K. A.
Manning, C. A.
Karmakar, S. K.
Wang, J. F.
Weyand, C. M.
Pettit, A. R.
Gravallese, E. M.
Title Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL
Journal name Genes and Immunity   Check publisher's open access policy
ISSN 1466-4879
Publication date 2013-07-01
Sub-type Article (original research)
DOI 10.1038/gene.2013.29
Open Access Status Not Open Access
Volume 14
Issue 5
Start page 336
End page 345
Total pages 10
Place of publication London, United Kingdom
Publisher Nature
Language eng
Abstract Receptor activator of nuclear factor-kappaB-ligand (RANKL), encoded by the gene TNFSF11, is required for osteoclastogenesis, and its expression is upregulated in pathologic bone loss. Transcript variants of TNFSF11 messenger RNA (mRNA) have been described that encode a membrane-bound and a putative secreted form of RANKL. We identify a TNFSF11 transcript variant that extends the originally identified transcript encoding secreted RANKL. We demonstrate that this TNFSF11 transcript variant is expressed by the human osteosarcoma cell line, Saos-2, and by both primary human T cells and Jurkat T cells. Of relevance to the production of RANKL in pathologic bone loss, expression of this secreted TNFSF11 transcript is upregulated in Jurkat T cells and primary human T cells upon activation. Furthermore, this transcript can be translated and secreted in Jurkat T cells in vitro and is able to support osteoclast differentiation. Our data highlight the complexity of the TNFSF11 genomic locus, and demonstrate the potential for the expression of alternate mRNA transcripts encoding membrane-bound and secreted forms of RANKL. Implications of alternate mRNA transcripts encoding different RANKL protein isoforms should be carefully considered and specifically examined in future studies, particularly those implicating RANKL in pathologic bone loss.
Keyword RANKL
Secreted RANKL
T cells
Inflammatory bone loss
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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