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PPAR Research
Volume 2009 (2009), Article ID 193413, 8 pages
http://dx.doi.org/10.1155/2009/193413
Research Article

Regulation of Translational Efficiency by Disparate 5 β€² -UTRs of PPAR 𝛾 Splice Variants

Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262, USA

Received 30 June 2009; Accepted 1 September 2009

Academic Editor: Mostafa Badr

Copyright © 2009 Shawn McClelland et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The PPAR- 𝛾 gene encodes for at least 7 unique transcripts due to alternative splicing of five exons in the 5 ξ…ž -untranslated region (UTR). The translated region is encoded by exons 1–6, which are identical in all isoforms. This study investigated the role of the 5 ξ…ž -UTR in regulating the efficiency with which the message is translated to protein. A coupled in vitro transcription-translation assay demonstrated that PPAR- 𝛾 1, - 𝛾 2, and - 𝛾 5 are efficiently translated, whereas PPAR- 𝛾 4 and - 𝛾 7 are poorly translated. An in vivo reporter gene assay using each 5 ξ…ž -UTR upstream of the firefly luciferase gene showed that the 5 ξ…ž -UTRs for PPAR- 𝛾 1, - 𝛾 2, and - 𝛾 4 enhanced translation, whereas the 5 ξ…ž -UTRs for PPAR- 𝛾 5 and - 𝛾 7 inhibited translation. Models of RNA secondary structure, obtained by the mfold software, were used to explain the mechanism of regulation by each 5 ξ…ž -UTR. In general, it was found that the translational efficiency was inversely correlated with the stability of the mRNA secondary structure, the presence of base-pairing in the consensus Kozak sequence, the number of start codons in the 5 ξ…ž -UTR, and the length of the 5 ξ…ž -UTR. A better understanding of posttranscriptional regulation of translation will allow modulation of protein levels without altering transcription.