Genome-Wide Identification of Alternatively Spliced mRNA Targets of Specific RNA-Binding Proteins

Robida, Mark D.; Rahn, Andrew; Singh, Ravinder

doi:10.1371/journal.pone.0000520

Cited by 20 publications

(20 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We therefore examined the splicing of six known regulators of alternative splicing: mub, Rm62, Psi, B52, sqd, and ps (Park et al 2004;Blanchette et al 2005;Robida et al 2007). All six genes had probes on the array and showed significant sex bias for the constitutive exons (supplemental Table 6).…”

Section: Resultsmentioning

confidence: 99%

Sex-Specific Splicing in Drosophila: Widespread Occurrence, Tissue Specificity and Evolutionary Conservation

et al. 2009

View full text Add to dashboard Cite

Many genes in eukaryotic genomes produce multiple transcripts through a variety of molecular mechanisms including alternative splicing. Alternatively spliced transcripts often encode functionally distinct proteins, indicating that gene regulation at this level makes an important contribution to organismal complexity. The multilevel splicing cascade that regulates sex determination and sex-specific development in Drosophila is a classical example of the role of alternative splicing in cell differentiation. Recent evidence suggests that a large proportion of genes in the Drosophila genome may be spliced in a sex-biased fashion, raising the possibility that alternative splicing may play a more general role in sexually dimorphic development and physiology. However, the prevalence of sex-specific splicing and the extent to which it is shared among genotypes are not fully understood. Genetic variation in the splicing of key components of the sex determination pathway is known to influence the expression of downstream target genes, suggesting that alternative splicing at other loci may also vary in functionally important ways. In this study, we used exon-specific microarrays to examine 417 multitranscript genes for evidence of sex-specific and genotype-specific splicing in 80 different genotypes of Drosophila melanogaster. Most of these loci showed sex-biased splicing, whereas genotype-specific splicing was rare. One hundred thirty-five genes showed different alternative transcript use in males vs. females. Real-time PCR analysis of 6 genes chosen to represent a broad range of biological functions showed that most sex-biased splicing occurs in the gonads. However, somatic tissues, particularly adult heads, also show evidence of sexspecific splicing. Comparison of splicing patterns at orthologous loci in seven Drosophila species shows that sexual biases in alternative exon representation are highly conserved, indicating that sex-specific splicing is an ancient feature of Drosophila biology. To investigate potential mechanisms of sex-biased splicing, we used realtime PCR to examine the expression of six known regulators of alternative splicing in males vs. females. We found that all six loci are themselves spliced sex specifically in gonads and heads, suggesting that regulatory hierarchies based on alternative splicing may be an important feature of sexual differentiation.

show abstract

Section: Resultsmentioning

confidence: 99%

Sex-Specific Splicing in Drosophila: Widespread Occurrence, Tissue Specificity and Evolutionary Conservation

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Such experiments produce complex phenotypes comprised of direct effects and a cascade of indirect effects that must be distinguished. Even for the well-studied Drosophila sex determination pathway, in which expression of the master regulator Sxl ultimately leads to a male or female form of the transcription factor Dsx (Baker 1989;Lopez 1998;Black 2003), we cannot begin to explain the integration of observed sex-specific transcription and splicing (Robida et al 2007;Telonis-Scott et al 2009). Part of this is due to Sxl regulation of translation as well as splicing (Penalva and Sanchez 2003), and another part is due to incomplete understanding of the sets of genes that respond to Tra and Dsx, and what the effects of those might be on sex-specific transcription and splicing.…”

Section: Discussionmentioning

confidence: 97%

Integration of a splicing regulatory network within the meiotic gene expression program of Saccharomyces cerevisiae

Munding¹,

Igel²,

Shiue³

et al. 2010

Genes Dev.

View full text Add to dashboard Cite

Splicing regulatory networks are essential components of eukaryotic gene expression programs, yet little is known about how they are integrated with transcriptional regulatory networks into coherent gene expression programs. Here we define the MER1 splicing regulatory network and examine its role in the gene expression program during meiosis in budding yeast. Mer1p splicing factor promotes splicing of just four pre-mRNAs. All four Mer1p-responsive genes also require Nam8p for splicing activation by Mer1p; however, other genes require Nam8p but not Mer1p, exposing an overlapping meiotic splicing network controlled by Nam8p. MER1 mRNA and three of the four Mer1p substrate pre-mRNAs are induced by the transcriptional regulator Ume6p. This unusual arrangement delays expression of Mer1p-responsive genes relative to other genes under Ume6p control. Products of Mer1p-responsive genes are required for initiating and completing recombination and for activation of Ndt80p, the activator of the transcriptional network required for subsequent steps in the program. Thus, the MER1 splicing regulatory network mediates the dependent relationship between the UME6 and NDT80 transcriptional regulatory networks in the meiotic gene expression program. This study reveals how splicing regulatory networks can be interlaced with transcriptional regulatory networks in eukaryotic gene expression programs.[Keywords: Regulated splicing; regulons; splicing-sensitive microarray; epistasis] Supplemental material is available at http://www.genesdev.org.

show abstract

“…Notch transcripts are also subject to Sxl regulation, but only in a subset of somatic cells (20)(21)(22). Additional candidate genes have been identified by bioinformatic approaches, but their biological relevance to germline differentiation has yet to be established (23,24). Thus, the Sxl target genes that mediate the GSC/CB cell fate switch remain to be discovered.…”

mentioning

confidence: 99%

Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis

Chau

Kulnane

Salz

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Drosophila ovarian germ cells require Sex-lethal (Sxl) to exit from the stem cell state and to enter the differentiation pathway. Sxl encodes a female-specific RNA binding protein and in somatic cells serves as the developmental switch gene for somatic sex determination and X-chromosome dosage compensation. None of the known Sxl target genes are required for germline differentiation, leaving open the question of how Sxl promotes the transition from stem cell to committed daughter cell. We address the mechanism by which Sxl regulates this transition through the identification of nanos as one of its target genes. Previous studies have shown that Nanos protein is necessary for GSC self-renewal and is rapidly down-regulated in the daughter cells fated to differentiate in the adult ovary. We find that this dynamic expression pattern is limited to female germ cells and is under Sxl control. In the absence of Sxl, or in male germ cells, Nanos protein is continuously expressed. Furthermore, this female-specific expression pattern is dependent on the presence of canonical Sxl binding sites located in the nanos 3′ untranslated region. These results, combined with the observation that nanos RNA associates with the Sxl protein in ovarian extracts and loss and gain of function studies, suggest that Sxl enables the switch from germline stem cell to committed daughter cell by posttranscriptional down-regulation of nanos expression. These findings connect sexual identity to the stem cell self-renewal/differentiation decision and highlight the importance of posttranscriptional gene regulatory networks in controlling stem cell behavior.

show abstract

Genome-Wide Identification of Alternatively Spliced mRNA Targets of Specific RNA-Binding Proteins

Cited by 20 publications

References 49 publications

Sex-Specific Splicing in Drosophila: Widespread Occurrence, Tissue Specificity and Evolutionary Conservation

Sex-Specific Splicing in Drosophila: Widespread Occurrence, Tissue Specificity and Evolutionary Conservation

Integration of a splicing regulatory network within the meiotic gene expression program of Saccharomyces cerevisiae

Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis

Contact Info

Product

Resources

About