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

Lai, C Benjamin, Zhang, Ying, Rogers, Sally L and Mager, Dixie L (2009) Creation of the two isoforms of rodent NKG2D was driven by a B1 retrotransposon insertion. Nucleic Acids Research, 37 (9). pp. 3032-43. doi:10.1093/nar/gkp174

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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.

Item Type: Article
Article Type: Article
Uncontrolled Keywords: REF2014 Submission
Related URLs:
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Divisions: Schools and Research Institutes > School of Education and Science
Research Priority Areas: Place, Environment and Community
Depositing User: Sally Rogers
Date Deposited: 10 Mar 2015 11:51
Last Modified: 31 Aug 2023 08:59

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