Sexy splicing: regulatory interplays governing sex determination from<i>Drosophila</i>to mammals

Lalli, Enzo; Ohe, Kenji; Latorre, Elisa; Bianchi, Marco E.; Sassone–Corsi, Paolo

doi:10.1242/jcs.00249

Cited by 36 publications

(27 citation statements)

References 35 publications

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“…Analysis of SREs affected by the exonic editing revealed that the most common abolished splicing regulatory element (SRE) is 5 ′ -AAGAA-3 ′ (47 times out of 267), which is recognized by TRA2A and TRA2B (transformer 2α and transformer 2β homolog, respectively), known activators of AS, which account for sex determination in Drosophila (Lalli et al 2003). The most common newly formed SRE is 5 ′ -GGGA-3 ′ (43 new appearances out of 317), a motif recognized by HNRNPF (regulators of splicing that play a role in splice site selection) (Martinez-Contreras et al 2006).…”

Section: Collection Of Editing Sitesmentioning

confidence: 99%

Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR)

Solomon

Oren

Safran

et al. 2013

RNA

109

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Alternative mRNA splicing is a major mechanism for gene regulation and transcriptome diversity. Despite the extent of the phenomenon, the regulation and specificity of the splicing machinery are only partially understood. Adenosine-to-inosine (A-to-I) RNA editing of pre-mRNA by ADAR enzymes has been linked to splicing regulation in several cases. Here we used bioinformatics approaches, RNA-seq and exon-specific microarray of ADAR knockdown cells to globally examine how ADAR and its A-to-I RNA editing activity influence alternative mRNA splicing. Although A-to-I RNA editing only rarely targets canonical splicing acceptor, donor, and branch sites, it was found to affect splicing regulatory elements (SREs) within exons. Cassette exons were found to be significantly enriched with A-to-I RNA editing sites compared with constitutive exons. RNAseq and exon-specific microarray revealed that ADAR knockdown in hepatocarcinoma and myelogenous leukemia cell lines leads to global changes in gene expression, with hundreds of genes changing their splicing patterns in both cell lines. This global change in splicing pattern cannot be explained by putative editing sites alone. Genes showing significant changes in their splicing pattern are frequently involved in RNA processing and splicing activity. Analysis of recently published RNA-seq data from glioblastoma cell lines showed similar results. Our global analysis reveals that ADAR plays a major role in splicing regulation. Although direct editing of the splicing motifs does occur, we suggest it is not likely to be the primary mechanism for ADAR-mediated regulation of alternative splicing. Rather, this regulation is achieved by modulating trans-acting factors involved in the splicing machinery.

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Section: Collection Of Editing Sitesmentioning

confidence: 99%

Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR)

Solomon

Oren

Safran

et al. 2013

RNA

109

View full text Add to dashboard Cite

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“…For detailed information on sex determination in D. melanogaster, the interested reader is referred to other reviews (MacDougall et al, 1995;Cline and Meyer, 1996;Schütt and Nöthiger, 2000; Sánchez et al, 2005). For other aspects on sex-determining mechanisms in other organisms see revisions by De Loof and Huybrechts (1998), Lalli et al (2003) and Manolakou et al (2006). This revision focuses on sex determination in the somatic component of the animal.…”

Section: The Sex-determining Genetic Cascade Of Drosophila Melanogastermentioning

confidence: 99%

Sex-determining mechanisms in insects

2008

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Sex determination refers to the developmental programme that commits the embryo to either the male or the female pathway. The animal kingdom possesses a wealth of mechanisms via which gender is decided, all of which are represented among the insects. This manuscript focuses on a number of insects for which genetic and molecular data regarding sex determination mechanisms are available. The sex determination genetic cascade of Drosophila melanogaster is first discussed, followed by an analysis of the sex determination genes of other dipteran and nondipteran insects. Representative examples of sex determination mechanisms that differ in their primary signal are also described. Finally, some evolutionary aspects of these mechanisms are discussed.

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“…Thus it may be that conceptual advances in our understanding of the molecular genetics of testes determination will involve determining how an already identified set of transcription factors interact with each other and with their target genes, rather than identifying additional transcription factors previously not associated with sex determination. Furthermore, as the Affimetrix GeneChip 1 Mouse Genome 430 2.0 array does not survey the non coding RNA transcriptome, addressing the possibility of additional control of mammalian sex determination at the post-transcriptional level must await further technical refinements (Lalli et al, 2003).…”

Section: Global Analysis Of Presumptive Pre-sertolimentioning

confidence: 99%

Presumptive pre‐sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation

Cory

Boyer

Pilon

et al. 2007

Molecular Reproduction Devel

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In mammals, the pre-Sertoli cell of the male genital ridge is the first cell type to display sex specific differentiation and differential gene expression. The genetic cascade driving the differentiationof pre-Sertoli cells and ultimately testis formationis beginning to be unravelled, but many questions remain. A better understanding of the transcriptome of pre-Sertoli cells immediately after sex determination is essential in order to further understand this differentiationprocess. A mouse model expressing Red Fluorescent Protein (RFP) under the control of a hybrid mouse/pig SRY promoter (HybSRYp-RFP) was used to purify cells from embryonic day 12.0 (e12.0) male genital ridges. To compare the transcriptomes of HybSRYp-RFP cell populations versus age matched whole female genital ridges, RNA was extracted and used to generate molecular probes that were hybridized onto Affymetrix Mouse Genome 430 2.0 microarrays. The expression of genes considered markers for pre-Sertoli cells, including Sox9, Mis, Dhh and Fgf9 were identified within the HybSRYp-RFP expressing cell population, while markers for germ cells (Oct4, SSEA-1) and endothelial cells (Ntrk3) were not identified. In contrast, markers for ovarian somatic cell expression, including Fst and Bmp2, were identified as overexpressed within the ovarian cell population. In a general fashion, genes identified as 2.5-fold over expressed in HybSRYp-RFP expressing cells coded notably for cell signalling and extra cellular proteins. The expression of Sox10, Stc2, Fgf18, Fgf13 and Wnt6 were further characterized via whole mount in situ hybridization (WISH) on male and female genital ridges between e11.5 and e14.5. Sox10, Fgf18, Fgf13 and Stc2 gene expression was detected within the male genital ridges while Wnt6 was found diffusely within both the male and female genital ridges. These data represent the earliest comprehensive microarray expression analysis of purified presumptive pre-Sertoli cells available to date. Mol. Reprod. Dev. 74: 1491-1504, 2007

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Sexy splicing: regulatory interplays governing sex determination fromDrosophilato mammals

Cited by 36 publications

References 35 publications

Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR)

Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR)

Sex-determining mechanisms in insects

Presumptive pre‐sertoli cells express genes involved in cell proliferation and cell signalling during a critical window in early testis differentiation

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