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Characterization of pps, a Modulator of Sxl Autoregulation in Drosophila melanogaster

Johnson, Matthew Logan

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2010, Doctor of Philosophy, Case Western Reserve University, Genetics.
The proper regulation of transcription and splicing is paramount for accurate expression of the genetic blueprint. Although transcription and splicing are coupled events, they have traditionally been examined separately. Without an integrated approach to scrutinizing these events, the mechanisms through which transcription may impact alternative splicing decisions remains unclear. Here, I report my analysis of a relatively unknown protein in Drosophila melanogaster, PPS (PROTEIN PARTNER OF SNF), which appears to link both transcription and splicing events. PPS was initially identified to interact directly with the U1/U2 snRNP protein, SNF (SANS-FILLE), yet contains a number of conserved motifs which suggest a role in transcription. In this work I demonstrate that pps is important for regulating alternative splicing of the master sex determining gene Sex-lethal (Sxl). Furthermore, my studies demonstrate that PPS is in a complex with other spliceosomal proteins that are known to block male exon inclusion within Sxl. Additionally, I find that PPS associates directly with the unspliced Sxl pre-mRNA. I go on to demonstrate that the association of PPS with splicing proteins involved in Sxl autoregulation occurs with the Sxl transcriptional unit co-transcriptionally. However, PPS is unique in that it is initially recruited to the promoter and remains associated throughout the transcriptional unit of Sxl, while the splicing proteins are only present at a limited number of sites. Furthermore, I present data demonstrating that PPS is physically associated with the transcription machinery. Based on these data I propose that PPS functions as a link between the transcriptional and splicing machinery and this link could facilitate the alternative splicing decisions in the Sxl pre-mRNA. These findings suggest a novel model of Sxl autoregulation where co-transcriptional actions participate in the regulation of alternative splicing events. Finally, I show PPS function is not limited to Sxl by demonstrating PPS associates with another SXL-regulated gene, transformer, and loss of pps function results in lethality to both sexes. Together these data suggest that PPS may play a more global role in the co-transcriptional control of alternative splicing.
Helen Salz, PhD (Advisor)
Hua Lou, PhD (Committee Chair)
Peter Harte, PhD (Committee Member)
Jo Ann Wise, PhD (Committee Member)
Erik Andrulis, PhD (Committee Member)
162 p.

Recommended Citations

Citations

  • Johnson, M. L. (2010). Characterization of pps, a Modulator of Sxl Autoregulation in Drosophila melanogaster [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1251947718

    APA Style (7th edition)

  • Johnson, Matthew. Characterization of pps, a Modulator of Sxl Autoregulation in Drosophila melanogaster. 2010. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1251947718.

    MLA Style (8th edition)

  • Johnson, Matthew. "Characterization of pps, a Modulator of Sxl Autoregulation in Drosophila melanogaster." Doctoral dissertation, Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1251947718

    Chicago Manual of Style (17th edition)