Human SSRP1 Has Spt16-dependent and -independent Roles in Gene Transcription

Li, Yanping; Zeng, Shelya X.; Landais, Igor; Lu, Hua

doi:10.1074/jbc.m603822200

Cited by 62 publications

(62 citation statements)

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“…Consistently, in mammals, SSRP1 has additional, SPT16-independent roles in RNAPII transcription (Antosch et al, 2012). Thus, SSRP1 can act as a coactivator of sequence-specific transcription factors (Spencer et al, 1999;Zeng et al, 2002), and transcript profiling revealed SSRP1-specific targets (Li et al, 2007). Moreover, Arabidopsis SSRP1, but not SPT16, is required for the action of the DNA demethylase DME in the central cell of the female gametophyte (Ikeda et al, 2011).…”

Section: Discussionmentioning

confidence: 71%

The Composition of the Arabidopsis RNA Polymerase II Transcript Elongation Complex Reveals the Interplay between Elongation and mRNA Processing Factors

et al. 2017

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Transcript elongation factors (TEFs) are a heterogeneous group of proteins that control the efficiency of transcript elongation of subsets of genes by RNA polymerase II (RNAPII) in the chromatin context. Using reciprocal tagging in combination with affinity purification and mass spectrometry, we demonstrate that in Arabidopsis thaliana, the TEFs SPT4/SPT5, SPT6, FACT, PAF1-C, and TFIIS copurified with each other and with elongating RNAPII, while P-TEFb was not among the interactors. Additionally, NAP1 histone chaperones, ATP-dependent chromatin remodeling factors, and some histone-modifying enzymes including Elongator were repeatedly found associated with TEFs. Analysis of double mutant plants defective in different combinations of TEFs revealed genetic interactions between genes encoding subunits of PAF1-C, FACT, and TFIIS, resulting in synergistic/epistatic effects on plant growth/development. Analysis of subnuclear localization, gene expression, and chromatin association did not provide evidence for an involvement of the TEFs in transcription by RNAPI (or RNAPIII). Proteomics analyses also revealed multiple interactions between the transcript elongation complex and factors involved in mRNA splicing and polyadenylation, including an association of PAF1-C with the polyadenylation factor CstF. Therefore, the RNAPII transcript elongation complex represents a platform for interactions among different TEFs, as well as for coordinating ongoing transcription with mRNA processing.

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Section: Discussionmentioning

confidence: 71%

The Composition of the Arabidopsis RNA Polymerase II Transcript Elongation Complex Reveals the Interplay between Elongation and mRNA Processing Factors

et al. 2017

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“…The first study analyzed global gene expression profiles in lung adenocarcinoma cells upon inhibition of either SSRP1 or SPT16 expression using shRNA, and found that there is a set of genes that are differentially dependent on either SSRP1 or SPT16 expression. 12 The second paper demonstrated that SSRP1, but not SPT16, is involved in regulating spindle formation during mitosis. 28 It should be noted, however, that neither of these studies unequivocally established that FACT subunits act independently.…”

Section: Discussionmentioning

confidence: 99%

“…11, 12 Despite these intriguing functions (and the possibility of additional functions that have yet to be described), FACT has been primarily studied in single cell models, such as yeast and cultured human tumor cells, and the physiological roles of FACT in multicellular organisms remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells

Safina

Garcia

Commane³

et al. 2013

Cell Cycle

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rePortFacilitates chromatin transcription (FaCt) is a chromatin remodeling complex with two subunits: SSrP1 and SPt16. Mechanisms controlling FaCt levels are of interest, since the complex is not expressed in most differentiated cells, but is frequently upregulated in cancer, particularly in poorly differentiated, aggressive tumors. Moreover, inhibition of FaCt expression or function in tumor cells interferes with their survival. Here we demonstrate that SSrP1 and SPt16 protein levels decline upon induction of cellular differentiation or senescence in vitro and that similar declines in protein levels for both SSrP1 and SPt16 occur upon rNai-mediated knockdown of either SSrP1 or SPt16. the interdependence of SSrP1 and SPt16 protein levels was found to be due to their association with SSrP1 and SPt16 mrNas, which stabilizes the proteins. In particular, presence of SSrP1 mrNa is critical for SPt16 protein stability. In addition, binding of SSrP1 and SPt16 mrNas to the FaCt complex increases the stability and efficiency of translation of the mrNas. these data support a model in which the FaCt complex is stable when SSrP1 mrNa is present, but quickly degrades when SSrP1 mrNa levels drop. In the absence of FaCt complex, SSrP1 and SPt16 mrNas are unstable and inefficiently translated, making reactivation of FaCt function unlikely in normal cells. thus, we have described a complex and unusual mode of regulation controlling cellular FaCt levels that results in amplified and stringent control of FaCt activity. the FaCt dependence of tumor cells suggests that mechanisms controlling FaCt levels could be targeted for anticancer therapy.

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“…Intriguingly, Spt16-depleted yeast exhibits a G 1 phase delay, pointing to specific functions of either FACT component (MorilloHuesca et al, 2010). Similarly, human SSRP1 and SPT16 (SUPT16H) can regulate largely overlapping, but also distinct targets (Li et al, 2007).…”

Section: Ssrp1a Promotes Cell Cycle Progression In the Digestive Systmentioning

confidence: 99%

Ssrp1a controls organogenesis by promoting cell cycle progression and RNA synthesis

Koltowska¹,

Apitz²,

Stamataki³

et al. 2013

Development

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SUMMARYTightly controlled DNA replication and RNA transcription are essential for differentiation and tissue growth in multicellular organisms. Histone chaperones, including the FACT (facilitates chromatin transcription) complex, are central for these processes and act by mediating DNA access through nucleosome reorganisation. However, their roles in vertebrate organogenesis are poorly understood. Here, we report the identification of zebrafish mutants for the gene encoding Structure specific recognition protein 1a (Ssrp1a), which, together with Spt16, forms the FACT heterodimer. Focussing on the liver and eye, we show that zygotic Ssrp1a is essential for proliferation and differentiation during organogenesis. Specifically, gene expression indicative of progressive organ differentiation is disrupted and RNA transcription is globally reduced. Ssrp1a-deficient embryos exhibit DNA synthesis defects and prolonged S phase, uncovering a role distinct from that of Spt16, which promotes G 1 phase progression. Gene deletion/replacement experiments in Drosophila show that Ssrp1b, Ssrp1a and N-terminal Ssrp1a, equivalent to the yeast homologue Pob3, can substitute Drosophila Ssrp function. These data suggest that (1) Ssrp1b does not compensate for Ssrp1a loss in the zebrafish embryo, probably owing to insufficient expression levels, and (2) despite fundamental structural differences, the mechanisms mediating DNA accessibility by FACT are conserved between yeast and metazoans. We propose that the essential functions of Ssrp1a in DNA replication and gene transcription, together with its dynamic spatiotemporal expression, ensure organ-specific differentiation and proportional growth, which are crucial for the forming embryo.

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Human SSRP1 Has Spt16-dependent and -independent Roles in Gene Transcription

Cited by 62 publications

References 50 publications

The Composition of the Arabidopsis RNA Polymerase II Transcript Elongation Complex Reveals the Interplay between Elongation and mRNA Processing Factors

The Composition of the Arabidopsis RNA Polymerase II Transcript Elongation Complex Reveals the Interplay between Elongation and mRNA Processing Factors

Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells

Ssrp1a controls organogenesis by promoting cell cycle progression and RNA synthesis

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