Expression analysis of the polypyrimidine tract binding protein (PTBP1) and its paralogs PTBP2 and PTBP3 during Xenopus tropicalis embryogenesis

Noiret, Maud; Audic, Yann; Hardy, Serge

doi:10.1387/ijdb.120017sh

Cited by 11 publications

(10 citation statements)

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“…PTBP2, a member of PTB (polypyrimidine tract binding protein) family of RNA-binding proteins which plays a critical role in development through the regulation of post-transcriptional events, is expressed in the nervous system including the brain, the neural retina and the spinal cord and the intermediate mesoderm [31]. PTBP2 regulates the generation of neuronal precursors in the embryonic brain by repressing adult-specific splicing [32], but the function involved in OS development has not been discovered.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of differentially expressed genes in osteosarcoma based on gene expression data

Yang

Chen

et al. 2014

BMC Med Genet

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BackgroundTo uncover the genes involved in the development of osteosarcoma (OS), we performed a meta-analysis of OS microarray data to identify differentially expressed genes (DEGs) and biological functions associated with gene expression changes between OS and normal control (NC) tissues.MethodsWe used publicly available GEO datasets of OS to perform a meta-analysis. We performed Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein-Protein interaction (PPI) networks analysis.ResultsEight GEO datasets, including 240 samples of OS and 35 samples of controls, were available for the meta-analysis. We identified 979 DEGs across the studies between OS and NC tissues (472 up-regulated and 507 down-regulated). We found GO terms for molecular functions significantly enriched in protein binding (GO: 0005515, P = 3.83E-60) and calcium ion binding (GO: 0005509, P = 3.79E-13), while for biological processes, the enriched GO terms were cell adhesion (GO:0007155, P = 2.26E-19) and negative regulation of apoptotic process (GO: 0043066, P = 3.24E-15), and for cellular component, the enriched GO terms were cytoplasm (GO: 0005737, P = 9.18E-63) and extracellular region (GO: 0005576, P = 2.28E-47). The most significant pathway in our KEGG analysis was Focal adhesion (P = 5.70E-15). Furthermore, ECM-receptor interaction (P = 1.27E-13) and Cell cycle (P = 4.53E-11) are found to be highly enriched. PPI network analysis indicated that the significant hub proteins containing PTBP2 (Degree = 33), RGS4 (Degree = 15) and FXYD6 (Degree = 13).ConclusionsOur meta-analysis detected DEGs and biological functions associated with gene expression changes between OS and NC tissues, guiding further identification and treatment for OS.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of differentially expressed genes in osteosarcoma based on gene expression data

Yang

Chen

et al. 2014

BMC Med Genet

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“…Here, we used the Xenopus model to address how differential levels of expression of the PTBP1 homologue, ptbp1, are achieved in two different tissues: the epidermis, where ptbp1 mRNA is abundant, and the somites, where it is barely present (24). We hypothesized that the RBP Esrp1 (also known as Rbm35a) could contribute to the high level of ptbp1 expression.…”

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A Posttranscriptional Mechanism That Controls Ptbp1 Abundance in the Xenopus Epidermis

Méreau

Anquetil

Lerivray

et al. 2015

Molecular and Cellular Biology

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The output of alternative splicing depends on the cooperative or antagonistic activities of several RNA-binding proteins (RBPs), like Ptbp1 and Esrp1 in Xenopus. Fine-tuning of the RBP abundance is therefore of prime importance to achieve tissue-or cellspecific splicing patterns. Here, we addressed the mechanisms leading to the high expression of the ptbp1 gene, which encodes Ptbp1, in Xenopus epidermis. Two splice isoforms of ptbp1 mRNA differ by the presence of an alternative exon 11, and only the isoform including exon 11 can be translated to a full-length protein. In vivo minigene assays revealed that the nonproductive isoform was predominantly produced. Knockdown experiments demonstrated that Esrp1, which is specific to the epidermis, strongly stimulated the expression of ptbp1 by favoring the productive isoform. Consequently, knocking down esrp1 phenocopied ptbp1 inactivation. Conversely, Ptbp1 repressed the expression of its own gene by favoring the nonproductive isoform. Hence, a complex posttranscriptional mechanism controls Ptbp1 abundance in Xenopus epidermis: skipping of exon 11 is the default splicing pattern, but Esrp1 stimulates ptbp1 expression by favoring the inclusion of exon 11 up to a level that is limited by Ptbp1 itself. These results decipher a posttranscriptional mechanism that achieves various abundances of the ubiquitous RBP Ptbp1 in different tissues.A lternative splicing relies on the selection of different splice sites within a pre-mRNA and allows different mRNA isoforms to be produced from a given gene. Deep sequencing of mRNA across several human tissues has revealed that up to 94% of human gene products are subject to alternative splicing, indicating that it is a widespread means of regulating gene expression. The selection of the splice isoforms of an mRNA is specific to cell types or developmental stages. Hence, alternative splicing promotes specific proteomes that in turn specify the cellular identity (1, 2).cis-Acting regulatory elements within a pre-mRNA control alternative splicing. A single alternative splice event is generally under the control of a combination of positive and negative controls. Several RNA-binding proteins (RBPs), including those of the hn-RNP and SR subfamilies, directly interact with these cis-acting regulatory sequences and either cooperate or antagonize to dictate the final outcome of the splicing reaction (3). The tissue specificity of alternative splicing can rely on the tissue-specific expression of RBPs that regulates pre-mRNA splicing, as shown for NOVA-1 in neurons (4). It can also be achieved through small changes in the relative levels or activities of ubiquitous factors (5). For example, the RBPs TIA1 and PTBP1 play antagonistic roles in the control of FAS alternative splicing (6), and it can be anticipated that subtle tissue-specific changes in the TIA1-to-PTBP1 ratio may lead to significant changes in the splicing pattern of FAS. Phosphorylations and, potentially, cell-type-specific phosphorylations have also been shown to affect the local ...

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“…Embryos were bleached in 1.2 % hydrogen peroxide in SSC. For detailed analysis embryos treated for whole mount in situ hybridization and stored in PBST were embedded in 5 % agar and sectioned on a LEICA VT 1200S vibratome at 50 mm thickness as described in (Noiret et al, 2012). Pictures were taken on a Leica Z16 APO macroscope.…”

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zfp36 expression delineates both myeloid cells and cells localized to the fusing neural folds in Xenopus tropicalis

2014

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Regulatory RNA binding proteins allow for specific control of gene expression in a very dynamic manner. In mammals ZFP36, formerly known as Tristetraprolin, controls the inflammatory response by binding to an AU-rich element located in the 3' untranslated region of its target mRNAs. The developping embryo relies on a population of primitive macrophages to ensure proper immunity. Although the role of zfp36 in adult immunity has been extensively studied, its expression in the developing immune system has been poorly documented. Here, we have used whole mount in situ hybridization with a 3' UTR specific probe to address the expression of zfp36 in developing Xenopus tropicalis embryos. We have shown that zfp36 is expressed in two distinct cellular populations. First, it is a new marker of primititive myeloid cells, being coexpressed with the myeloid marker mpo. Therefore this early expression may suggest a role for zfp36 in macrophage differentiation and activation. In addition, a second cell population was found to transiently express zfp36, but not mpo, along the fusing neural folds and may correspond to cells undergoing autophagy during neural tube closure. KEY WORDS: RNA binding proteins, Xenopus tropicalis, embryonic immunityZFP36 formerly known as Tristetraprolin (TTP) (Lai et al., 2014) belongs to a family of RNA binding Zinc Fingers containing proteins which is composed of 3 members in humans, ZFP36, ZFP36L1 and ZFP36L2. In Xenopus laevis, a fourth member previously called C3H4 and named Zfp36L4 has been identified (Belloc and Méndez, 2008;De et al., 1999;Tréguer et al., 2013).Functionally, ZFP36 has been shown to regulate post-transcriptionnally the inflammatory response by controling the expression level of inflammatory factors such as TNF-alpha (Carballo et al., 1998) or GM-CSF (Carballo et al., 2000. Mice constitutively deficient for ZFP36, albeit apparently normal at birth develop a debilitating inflammatory response (Taylor et al., 1996). ZFP36 acts through the specific binding to AU-rich element present in the 3'UTR of the targeted mRNAs and triggers their destabilization .Extensive work has been conducted to address the function of ZFP36 in the regulation of inflammatory processes while its expression in the developing immune system has been loosely documented. Xenopus is a useful model system to study the multiple steps of early immune system development (Ciau-Uitz et al., 2010). In Xenopus embryos, primitive hematopoiesis is initiated in a ventral region termed the ventral blood island (VBI) that is the equivalent of the mammalian extraembryonic yolk sac. The Int. J. Dev. Biol. 58: 751-755 (2014) VBI is composed of two areas, the anterior VBI (aVBI) and the posterior VBI (pVBI) that give rises to different cell populations. The aVBI originates from blastomeres C1D1 and comprises an hemangioblast-like population of cells expressing both blood and endothelial cell markers at stage 14. Yet, it has recently been shown that in normal situation the aVBI will only produce blood cells (Myers a...

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Expression analysis of the polypyrimidine tract binding protein (PTBP1) and its paralogs PTBP2 and PTBP3 during Xenopus tropicalis embryogenesis

Cited by 11 publications

References 9 publications

Meta-analysis of differentially expressed genes in osteosarcoma based on gene expression data

Meta-analysis of differentially expressed genes in osteosarcoma based on gene expression data

A Posttranscriptional Mechanism That Controls Ptbp1 Abundance in the Xenopus Epidermis

zfp36 expression delineates both myeloid cells and cells localized to the fusing neural folds in Xenopus tropicalis

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