Autoregulation of transformer-2 alternative splicing is necessary for normal male fertility in Drosophila.

Genetics
M E McGuffinWilliam Mattox

Abstract

In the male germline of Drosophila the transformer-2 protein is required for differential splicing of pre-mRNAs from the exuperantia and att genes and autoregulates alternative splicing of its own pre-mRNA. Autoregulation of TRA-2 splicing results in production of two mRNAs that differ by the splicing/retention of the M1 intron and encode functionally distinct protein isoforms. Splicing of the intron produces an mRNA encoding TRA-2(226), which is necessary and sufficient for both male fertility and regulation of downstream target RNAs. When the intron is retained, an mRNA is produced encoding TRA-2(179), a protein with no known function. We have previously shown that repression of M1 splicing is dependent on TRA-2(226), suggesting that this protein quantitatively limits its own expression through a negative feedback mechanism at the level of splicing. Here we examine this idea, by testing the effect that variations in the level of tra-2 expression have on the splicing of M1 and on male fertility. Consistent with our hypothesis, we observe that as tra-2 gene dosage is increased, smaller proportions of TRA-2(226) mRNA are produced, limiting expression of this isoform. Feedback regulation is critical for male fertility, since it i...Continue Reading

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Citations

Nov 5, 2003·Genesis : the Journal of Genetics and Development·Emmanual UnniWilliam Mattox
Jul 16, 2003·Molecular and Cellular Biology·Dawn S ChandlerWilliam Mattox
Jun 23, 1999·Current Opinion in Genetics & Development·J P Venables, I Eperon
May 15, 2010·BMC Evolutionary Biology·Francesca SarnoLucas Sánchez
Aug 30, 2011·Molecular Biology and Evolution·Julian P VenablesJamal Tazi
Sep 13, 2011·Nucleic Acids Research·Julian P VenablesFrançois Juge
Nov 15, 2011·Insect Biochemistry and Molecular Biology·Marc F ScheteligAlfred M Handler

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