PTB-associated splicing factor regulates growth factor-stimulated gene expression in mammalian cells

Urban, Randall J.; Bodenburg, Yvonne H.

doi:10.1152/ajpendo.00174.2002

Cited by 29 publications

(18 citation statements)

References 16 publications

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“…Additional functions of SRP20 include polyadenylation (Lou et al 1998) and nucleocytoplasmic export of mRNA (Huang and Steitz 2001). PSF participates in the nuclear retention of misedited RNA (Zhang and Carmichael 2001), repression of transcription (Mathur et al 2001;Urban and Bodenburg 2002), and DNA repair (for review, see Shav-Tal and Zipori 2002;Bladen et al 2005). Further work will be necessary to determine the importance of the Srp20 and Psf mRNA expression changes on alternative splicing and memory formation.…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation

Antunes-Martins¹,

Mizuno²,

Irvine³

et al. 2007

Learn. Mem.

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Gene transcription is required for long-term memory (LTM) formation. LTM formation is impaired in a male-specific manner in mice lacking either of the two Ca 2+ /calmodulin-dependent kinase kinase (Camkk) genes. Since altered transcription was suggested to cause these impairments in LTM formation, we used microarrays to screen for CaMKK␤-dependent gene expression changes. Here we show that the hippocampal mRNA expression of two splicing factors, splicing factor arginine/serine-rich 3 (Sfrs3/Srp20) and polypyrimidine tract-binding protein-associated splicing factor (Psf), is altered in CaMKK␤-deficient males. In wild-type (WT) mice, the basal expression level in the hippocampus is higher in males than in females, and the sex difference in Srp20 expression is detectable before puberty. Training in two hippocampus-dependent learning tasks, the spatial version of the Morris water maze (MWM) and background contextual fear conditioning, increases the hippocampal mRNA expression of both splicing factors in WT males. However, the increase in Srp20 mRNA expression occurs only in males and not in females, whereas the up-regulation of Psf expression occurs in both sexes. Importantly, control experiments demonstrate that the up-regulation of both splicing factors is specific for the learned associations after contextual fear conditioning. In summary, we provide the first evidence for a regulation of splicing factors during LTM formation and we suggest that alternative splicing contributes to sex differences in LTM formation.

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Section: Discussionmentioning

confidence: 99%

Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation

Antunes-Martins¹,

Mizuno²,

Irvine³

et al. 2007

Learn. Mem.

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“…31,32 Besides splicing, PSF has also been implicated in many other nuclear events. It has been shown to act as a transcriptional regulator in several different cases, such as regulation of growth factor stimulated gene expression, 33,34 as a corepressor acting through Sin3A to recruit histone deacetylases (HDACs) and induce silencing, 35 and as part of a complex that activates the human CYP17 promoter in response to cAMP stimulation. 36,37 PSF has also been implicated in the regulation of topoisomerase I activity, 27,38 as a DNA doublestranded break repair factor, 39 and in nuclear retention of hyper-edited RNAs.…”

Section: Introductionmentioning

confidence: 99%

The Splicing Factor PSF is Part of a Large Complex That Assembles in the Absence of pre-mRNA and Contains All 5 snRNPs

Peng¹,

Hawkins²,

Link³

et al. 2006

RNA Biology

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Previously published online as a RNA Biology E-publication: http://www.landesbioscience.com/journals/rnabiology/abstract.php?id=3017 KEY WORDS Research PaperThe Splicing Factor PSF is Part of a Large Complex that Assembles in the Absence of pre-mRNA and Contains All 5 snRNPs ABSTRACT PSF (PTB-associated splicing factor) is a large nuclear protein that has been implicated in numerous processes including transcription and RNA splicing. It has been shown to directly associate with U5 snRNA and has also been found within numerous purified splicing complexes. Here, we show that when HeLa nuclear extracts are adjusted to splicing conditions, PSF is found as part of a large complex that contains all five snRNPs and most known splicing factors. Formation of the complex does not require addition of exogenous pre-mRNA substrate and occurs at 4˚C but is salt sensitive. Sedimentation experiments and identification of individual components by mass spectrometry revealed association with multiple nuclear factors, most of which overlap with spliceosome components.

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“…The 12 DNAs bound to PSF in NIH/3T3 and B16F10 cells, as shown by a ChIP assay (Fig. 2); the P450scc gene had been identified as a PSF-binding gene in earlier studies (4,6). We chose the Rab23 gene, a member the RAS gene family (10,11), to analyze the role of PSF and VL30-1 RNA in the regulation of proto-oncogene transcription in mice.…”

Section: Resultsmentioning

confidence: 95%

Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA

Wang

Cui

Zhang

et al. 2009

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

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cancer therapy ͉ Rab23 ͉ regulatory RNA ͉ tumor suppression P receding studies have described a reversible mechanism controlling gene transcription that involves PSF protein (1) and VL30-1 RNA, a member of the VL30 family of mouse retroelement noncoding RNAs (2, 3). PSF contains a DNAbinding domain (DBD) that binds and represses transcription of genes that have a PSF-binding site (4-6) and 2 RNA-binding domains (RBDs) that bind VL30-1 RNA, forming a PSF-RNA complex that dissociates from a gene and activates transcription (5-7). Increasing expression of PSF in a human tumor cell suppressed tumorigenesis (6), and ectopic expression of VL30-1 RNA in a human tumor cell promoted metastasis (3). VL30 RNAs are expressed in virtually all tissues of adult mice (8) and are associated with Ras-mediated transformation of mouse fibroblast cells (9). Here, we extend our studies of the function of PSF and VL30-1 RNA to the regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice. The results indicate that PSF is a major tumor-suppressor protein and VL30-1 RNA is a major tumor-promoter RNA in mice. ResultsExpression of PSF and VL30 -1 RNA in NIH/3T3 and B16F10 Cell Lines.NIH/3T3 and B16F10 cells were transfected with a transgene encoding PSF (NIH/3T3-PSF1 and B16F10-PSF1 lines) or VL30-1 RNA (NIH/3T3-VL301 line) or with a plasmid encoding a shRNA that causes degradation of PSF mRNA (NIH/ 3T3-PSF2 line) or VL30 -1 RNA (NIH/3T3-VL302 and B16F10-VL302 lines). The control lines were transfected with an empty plasmid pcDNA3.1(ϩ) (NIH/3T3-pcDNA3.1 and B16F10-pcDNA3.1 cell lines) or a plasmid encoding shLuciferase (NIH/3T3-shLuc and B16F10-shLuc lines). The NIH/ 3T3 and B16F10 cell lines were assayed for expression of PSF mRNA and VL30-1 RNA ( Fig. 1 and Table 1) and PSF protein (Fig. 1).Binding of PSF to the Regulatory DNAs of Mouse Genes. Chromatin fragments from NIH/3T3 cells were coimmunoprecipitated with anti-PSF antibody, and the DNAs in the fragments were tested for hybridization to a mouse gene-promoter chip (NimbleGen; Roche) that contains 385,000 regulatory DNAs from the mouse genome. A total of 57 DNA fragments were identified by chip assay, of which 12 mapped to characterized mouse coding genes [supporting information (SI) Tables S1 and S2]. The 12 DNAs bound to PSF in NIH/3T3 and B16F10 cells, as shown by a ChIP assay (Fig. 2); the P450scc gene had been identified as a PSF-binding gene in earlier studies (4, 6). We chose the Rab23 gene, a member the RAS gene family (10,11), to analyze the role of PSF and VL30-1 RNA in the regulation of proto-oncogene transcription in mice. (Table 1). Binding of Rab23 DNA to PSF is higher in NIH/3T3-PSF1 and B16F10-PSF1 cells and lower in NIH/3T3-PSF2 cells than in NIH/3T3 or B16F10 control cells (Fig. 3A). (ii) Transcription of Rab23 was analyzed in the same cell lines by RT-PCR. Transcription is lower in NIH/3T3-PSF1 and B16F10-PSF1 cells and higher in NIH/3T3-PSF2 cells than in NIH/3T3 or B16F10 control cells (Fig. 3B). The results indicate that PSF bin...

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PTB-associated splicing factor regulates growth factor-stimulated gene expression in mammalian cells

Cited by 29 publications

References 16 publications

Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation

Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation

The Splicing Factor PSF is Part of a Large Complex That Assembles in the Absence of pre-mRNA and Contains All 5 snRNPs

Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA

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