Reference Report

Reference
Citation	Johnson, M.L., Nagengast, A.A., Salz, H.K. (2010). PPS, a Large Multidomain Protein, Functions with Sex-Lethal to Regulate Alternative Splicing in Drosophila. PLoS Genet. 6(3): e1000872. (Export to RIS)
FlyBase ID	FBrf0210202
Publication Type	Research paper
PubMed ID	20221253
PubMed Abstract	Alternative splicing controls the expression of many genes, including the Drosophila sex determination gene Sex-lethal (Sxl). Sxl expression is controlled via a negative regulatory mechanism where inclusion of the translation-terminating male exon is blocked in females. Previous studies have shown that the mechanism leading to exon skipping is autoregulatory and requires the SXL protein to antagonize exon inclusion by interacting with core spliceosomal proteins, including the U1 snRNP protein Sans-fille (SNF). In studies begun by screening for proteins that interact with SNF, we identified PPS, a previously uncharacterized protein, as a novel component of the machinery required for Sxl male exon skipping. PPS encodes a large protein with four signature motifs, PHD, BRK, TFS2M, and SPOC, typically found in proteins involved in transcription. We demonstrate that PPS has a direct role in Sxl male exon skipping by showing first that loss of function mutations have phenotypes indicative of Sxl misregulation and second that the PPS protein forms a complex with SXL and the unspliced Sxl RNA. In addition, we mapped the recruitment of PPS, SXL, and SNF along the Sxl gene using chromatin immunoprecipitation (ChIP), which revealed that, like many other splicing factors, these proteins bind their RNA targets while in close proximity to the DNA. Interestingly, while SNF and SXL are specifically recruited to their predicted binding sites, PPS has a distinct pattern of accumulation along the Sxl gene, associating with a region that includes, but is not limited to, the SxlPm promoter. Together, these data indicate that PPS is different from other splicing factors involved in male-exon skipping and suggest, for the first time, a functional link between transcription and SXL-mediated alternative splicing. Loss of zygotic PPS function, however, is lethal to both sexes, indicating that its role may be of broad significance.
DOI	10.1371/journal.pgen.1000872
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Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS Genet.
Title	PLoS Genetics
Publication Year	2005-
ISBN/ISSN	1553-7404 1553-7390
Data from Reference
Aberrations (3)
	Df(2L)D1 Df(3R)Exel7316 Df(3R)pps¹
Alleles (9)
	CG17202^+tJa CG17202^unspecified da¹ da² fl(2)d² pps^+tJa Sxl^f1 Sxl^fP7B0 U2af38^ΔE18
Constructs (2)
	P{CG17202^+tJa} P{pps^+tJa}
Genes (15)
	Cdk7 CG17202 da Dip-C fl(2)d Pc pps Scgβ snf snRNP-U1-70K Spf45 Sxl tra U2A U2af38
Insertions (2)
	PBac{WH}CG17202^f01979 PBac{WH}Dip-C^f00706
Natural transposons (1)
	P-element