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Nucleic Acids Research Advance Access originally published online on March 20, 2009
Nucleic Acids Research 2009 37(9):3032-3043; doi:10.1093/nar/gkp174
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Nucleic Acids Research, 2009, Vol. 37, No. 9 3032-3043
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Molecular Biology

Creation of the two isoforms of rodent NKG2D was driven by a B1 retrotransposon insertion

C. Benjamin Lai, Ying Zhang, Sally L. Rogers and Dixie L. Mager*

Terry Fox Laboratory, British Columbia Cancer Agency and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada

*To whom correspondence should be addressed. Tel: +1 604 675 8139; Fax: +1 604 877 0712; Email: dmager{at}bccrc.ca

Received September 17, 2008. Revised February 26, 2009. Accepted March 3, 2009.

The mouse gene for the natural killer (NK) cell-activating receptor Nkg2d produces two protein isoforms, NKG2D-S and NKG2D-L, which differ by 13 amino acids at the N-terminus and have different signalling capabilities. These two isoforms are produced through differential splicing, but their regulation has not been investigated. In this study, we show that rat Nkg2d has the same splicing pattern as that of the mouse, and we mapped transcriptional start sites in both species. We found that the splice forms arise from alternative promoters and that the NKG2D-L promoter is derived from a rodent B1 retrotransposon that inserted before mouse–rat divergence. This B1 insertion is associated with loss of a nearby splice acceptor site that subsequently allowed creation of the short NKG2D isoform found in mouse but not human. Transient reporter assays indicate that the B1 element is a strong promoter with no inherent lymphoid tissue-specificity. We have also identified different binding sites for the ETS family member GABP within both the mouse and rat B1 elements that are necessary for high-promoter activity and for full Nkg2d-L expression. These findings demonstrate that a retroelement insertion has led to gene-regulatory change and functional diversification of rodent NKG2D.


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