Nucleic Acids Research Advance Access originally published online on November 10, 2006
Nucleic Acids Research 2006 34(21):6256-6263; doi:10.1093/nar/gkl755
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Nucleic Acids Research, 2006, Vol. 34, No. 21 6256-6263
© 2006 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.
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Concentration dependent selection of targets by an SR splicing regulator results in tissue-specific RNA processing
Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center and Genes and Development Graduate Program, The University of Texas Graduate School of Biomedical Sciences Houston, TX 77030-4009, USA
*To whom correspondence should be addressed. Tel: +1 713 834 6329; Fax: +1 713 834 6339; Email: wmattox{at}mdanderson.org
Received July 21, 2006. Revised September 22, 2006. Accepted September 27, 2006.
The splicing factor Transformer-2 (Tra2) is expressed almost ubiquitously in Drosophila adults, but participates in the tissue-specific regulation of splicing in several RNAs. In somatic tissues Tra2 participates in the activation of sex-specific splice sites in doublesex and fruitless pre-mRNAs. In the male germline it affects splicing of other transcripts and represses removal of the M1 intron from its own pre-mRNA. Here we test the hypothesis that the germline specificity of M1 repression is determined by tissue-specific differences in Tra2 concentration. We find that Tra2 is expressed at higher levels in primary spermatocytes of males than in other cell types. Increased Tra2 expression in other tissues reduces viability in a manner consistent with known dose-dependent effects of excessive Tra2 expression in the male germline. Somatic cells were found to be competent to repress M1 splicing if the level of Tra2 transcription was raised above endogenous concentrations. This suggests not only that M1 repression is restricted to the germline by a difference in Tra2 transcription levels but also that the protein's threshold concentration for M1 regulation differs from that of doublesex and fruitless RNAs. We propose that quantitative differences in regulator expression can give rise to cell-type-specific restrictions in splicing.
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