Functions of DEAD box RNA helicases DDX5 and DDX17 in chromatin organization and transcriptional regulation

AbstractRing1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell–cell adhesions of breast cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast cancer.

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Association of the Cold Shock DEAD-Box RNA Helicase RhlE to the RNA Degradosome in Caulobacter crescentus

Journal of Bacteriology ◽

10.1128/jb.00135-17 ◽

2017 ◽

Vol 199 (13) ◽

Cited By ~ 15

Author(s):

Angel A. Aguirre ◽

Alexandre M. Vicente ◽

Steven W. Hardwick ◽

Daniela M. Alvelos ◽

Ricardo R. Mazzon ◽

...

Keyword(s):

Low Temperature ◽

Caulobacter Crescentus ◽

Immunoblot Analysis ◽

Rna Helicase ◽

Rnase E ◽

Rna Helicases ◽

Content Type ◽

Dead Box ◽

Rna Degradosome ◽

The Dead

ABSTRACT In diverse bacterial lineages, multienzyme assemblies have evolved that are central elements of RNA metabolism and RNA-mediated regulation. The aquatic Gram-negative bacterium Caulobacter crescentus, which has been a model system for studying the bacterial cell cycle, has an RNA degradosome assembly that is formed by the endoribonuclease RNase E and includes the DEAD-box RNA helicase RhlB. Immunoprecipitations of extracts from cells expressing an epitope-tagged RNase E reveal that RhlE, another member of the DEAD-box helicase family, associates with the degradosome at temperatures below those optimum for growth. Phenotype analyses of rhlE, rhlB, and rhlE rhlB mutant strains show that RhlE is important for cell fitness at low temperature and its role may not be substituted by RhlB. Transcriptional and translational fusions of rhlE to the lacZ reporter gene and immunoblot analysis of an epitope-tagged RhlE indicate that its expression is induced upon temperature decrease, mainly through posttranscriptional regulation. RNase E pulldown assays show that other proteins, including the transcription termination factor Rho, a second DEAD-box RNA helicase, and ribosomal protein S1, also associate with the degradosome at low temperature. The results suggest that the RNA degradosome assembly can be remodeled with environmental change to alter its repertoire of helicases and other accessory proteins. IMPORTANCE DEAD-box RNA helicases are often present in the RNA degradosome complex, helping unwind secondary structures to facilitate degradation. Caulobacter crescentus is an interesting organism to investigate degradosome remodeling with change in temperature, because it thrives in freshwater bodies and withstands low temperature. In this study, we show that at low temperature, the cold-induced DEAD-box RNA helicase RhlE is recruited to the RNA degradosome, along with other helicases and the Rho protein. RhlE is essential for bacterial fitness at low temperature, and its function may not be complemented by RhlB, although RhlE is able to complement for rhlB loss. These results suggest that RhlE has a specific role in the degradosome at low temperature, potentially improving adaptation to this condition.

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Rice APOPTOSIS INHIBITOR5 Coupled with Two DEAD-Box Adenosine 5′-Triphosphate-Dependent RNA Helicases Regulates Tapetum Degeneration

The Plant Cell ◽

10.1105/tpc.110.082636 ◽

2011 ◽

Vol 23 (4) ◽

pp. 1416-1434 ◽

Cited By ~ 80

Author(s):

Xingwang Li ◽

Xinqiang Gao ◽

Yi Wei ◽

Li Deng ◽

Yidan Ouyang ◽

...

Keyword(s):

Rna Helicases ◽

Dead Box

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Functional Characterization of DEAD-Box RNA Helicases in Arabidopsis thaliana under Abiotic Stress Conditions

Plant and Cell Physiology ◽

10.1093/pcp/pcn125 ◽

2008 ◽

Vol 49 (10) ◽

pp. 1563-1571 ◽

Cited By ~ 57

Author(s):

Jin Sun Kim ◽

Kyung Ae Kim ◽

Tae Rin Oh ◽

Chul Min Park ◽

Hunseung Kang

Keyword(s):

Arabidopsis Thaliana ◽

Abiotic Stress ◽

Functional Characterization ◽

Stress Conditions ◽

Rna Helicases ◽

Dead Box

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The embryonic RNA helicase gene (ERH): a new member of the DEAD box family of RNA helicases

Biochemical Journal ◽

10.1042/bj3080839 ◽

1995 ◽

Vol 308 (3) ◽

pp. 839-846 ◽

Cited By ~ 15

Author(s):

J Sowden ◽

W Putt ◽

K Morrison ◽

R Beddington ◽

Y Edwards

Keyword(s):

Expression Profile ◽

Sequence Similarity ◽

Rna Helicase ◽

Chromosome 1 ◽

Rna Helicases ◽

High Sequence Similarity ◽

Dead Box ◽

Isolation And Characterization ◽

Helicase Gene ◽

The Dead

DEAD box proteins share several highly conserved motifs including the characteristic Asp-Glu-Ala-Asp (D-E-A-D in the amino acid single-letter code) motif and have established or putative ATP-dependent RNA helicase activity. These proteins are implicated in a range of cellular processes that involve regulation of RNA function, including translation initiation, RNA splicing and ribosome assembly. Here we describe the isolation and characterization of an embryonic RNA helicase gene, ERH, which maps to mouse chromosome 1 and encodes a new member of the DEAD box family of proteins. The predicted ERH protein shows high sequence similarity to the testes-specific mouse PL10 and to the maternally acting Xenopus An3 helicase proteins. The ERH expression profile is similar, to that of An3, which localizes to the animal hemisphere of oocytes and is abundantly expressed in the embryo. ERH is expressed in oocytes and is a ubiquitous mRNA in the 9 days-post-conception embryo, and at later stages of development shows a more restricted pattern of expression in brain and kidney. The similarities in sequence and in expression profile suggest that ERH is the murine equivalent of the Xenopus An3 gene, and we propose that ERH plays a role in translational activation of mRNA in the oocyte and early embryo.

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The DEAD-Box RNA Helicases of Bacillus subtilis as a Model to Evaluate Genetic Compensation Among Duplicate Genes

Frontiers in Microbiology ◽

10.3389/fmicb.2018.02261 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

José Antonio González-Gutiérrez ◽

Diana Fabiola Díaz-Jiménez ◽

Itzel Vargas-Pérez ◽

Gabriel Guillén-Solís ◽

Jörg Stülke ◽

...

Keyword(s):

Bacillus Subtilis ◽

Duplicate Genes ◽

Rna Helicases ◽

Dead Box ◽

The Dead ◽

Genetic Compensation

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The histone variant H2A.Z and chromatin remodeler BRAHMA act coordinately and antagonistically to regulate transcription and nucleosome dynamics in Arabidopsis

10.1101/243790 ◽

2018 ◽

Author(s):

E. Shannon Torres ◽

Roger B. Deal

Keyword(s):

Transcriptional Regulation ◽

Transcription Factors ◽

Binding Sites ◽

Transcriptional Repression ◽

Nucleosome Positioning ◽

Chromatin Organization ◽

Histone H2a ◽

Nucleosome Dynamics ◽

Environmentally Responsive ◽

Context Specific

ABSTRACTPlants adapt to changes in their environment by regulating transcription and chromatin organization. The histone H2A variant H2A.Z and the SWI2/SNF2 ATPase BRAHMA have overlapping roles in positively and negatively regulating environmentally responsive genes in Arabidopsis, but the extent of this overlap was uncharacterized. Both have been associated with various changes in nucleosome positioning and stability in different contexts, but their specific roles in transcriptional regulation and chromatin organization need further characterization. We show that H2A.Z and BRM act both cooperatively and antagonistically to contribute directly to transcriptional repression and activation of genes involved in development and response to environmental stimuli. We identified 8 classes of genes that show distinct relationships between H2A.Z and BRM and their roles in transcription. We found that H2A.Z contributes to a range of different nucleosome properties, while BRM stabilizes nucleosomes where it binds and destabilizes and/or repositions flanking nucleosomes. H2A.Z and BRM contribute to +1 nucleosome destabilization, especially where they coordinately regulate transcription. We also found that at genes regulated by both BRM and H2A.Z, both factors overlap with the binding sites of light-regulated transcription factors PIF4, PIF5, and FRS9, and that some of the FRS9 binding sites are dependent on H2A.Z and BRM for accessibility. Collectively, we comprehensively characterized the antagonistic and cooperative contributions of H2A.Z and BRM to transcriptional regulation, and illuminated their interrelated roles in chromatin organization. The variability observed in their individual functions implies that both BRM and H2A.Z have more context-specific roles within diverse chromatin environments than previously assumed.

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DEAD-box RNA helicases in Arabidopsis thaliana: establishing a link between quantitative expression, gene structure and evolution of a family of genes

Plant Biotechnology Journal ◽

10.1111/j.1467-7652.2004.00084.x ◽

2004 ◽

Vol 2 (5) ◽

pp. 401-415 ◽

Cited By ~ 37

Author(s):

Annaïck Mingam ◽

Claire Toffano-Nioche ◽

Véronique Brunaud ◽

Nathalie Boudet ◽

Martin Kreis ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

Gene Structure ◽

Rna Helicases ◽

Quantitative Expression ◽

Dead Box

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The DEAD Box Protein DP103 Is a Regulator of Steroidogenic Factor-1

Molecular Endocrinology ◽

10.1210/mend.15.1.0580 ◽

2001 ◽

Vol 15 (1) ◽

pp. 69-79 ◽

Cited By ~ 43

Author(s):

Qinglin Ou ◽

Jean-François Mouillet ◽

Xiaomei Yan ◽

Christoph Dorn ◽

Peter A. Crawford ◽

...

Keyword(s):

Transcriptional Repression ◽

Transcriptional Activity ◽

Point Mutations ◽

Hypothalamic Nucleus ◽

Rna Helicases ◽

Interacting Protein ◽

Steroidogenic Factor 1 ◽

Dead Box ◽

The Dead ◽

Repression Domain

Abstract The nuclear receptor steroidogenic factor-1 (SF-1) is essential for development of the gonads, adrenal gland, and the ventromedial hypothalamic nucleus. It also regulates the expression of pivotal steroidogenic enzymes and other important proteins in the reproductive system. We sought to elucidate the mechanisms that govern the transcriptional activity of SF-1. We demonstrate here that a previously uncharacterized domain, located C-terminal to the DNA binding domain of SF-1, exhibits transcriptional repression function. Point mutations in this domain markedly potentiate the transcriptional activity of native SF-1. Using an SF-1 region that spans this proximal repression domain as bait in a yeast two-hybrid system, we cloned an SF-1 interacting protein that is homologous to human DP103, a member of the DEAD box family of putative RNA helicases. DP103 directly interacts with the proximal repression domain of SF-1, and mutations in this domain abrogate its interaction with DP103. DP103 is expressed predominantly in the testis and is also expressed at a lower level in other steroidogenic and nonsteroidogenic tissues. Functionally, DP103 exhibits a native transcriptional repression function that localizes to the C-terminal region of the protein and represses the activity of wild-type, but not mutant, SF-1. Together, the physical and functional interaction of DP103 with a previously unrecognized repression domain within SF-1 represents a novel mechanism for regulation of SF-1 activity.

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