role of helicase in transcription

However, it is now thought that rather than being processive RNA helicases, several DExD/H box proteins may be acting as RNA chaperones, promoting the formation of optimal RNA structures through local RNA unwinding, or as RNPases by mediating RNAprotein association/dissociation (58). Interestingly it has been suggested recently that DP103 mediates repression of SF-1 transcriptional activity by promoting sumoylation of SF-1 via the PIAS E3 SUMO ligases, which in turn results in subnuclear relocalization of SF-1 to discrete nuclear foci (42). Wan C, Mahara S, Sun C, Doan A, Chua HK, Xu D, Bian J, Li Y, Zhu D, Sooraj D, Cierpicki T, Grembecka J, Firestein R. Sci Adv. Since p68/p72 stimulates the estrogen-induced activity of ER and also interacts with steroid receptor coactivator, SRC1, and the RNA coactivator, SRA, it was suggested that p68 might coactivate ER by mediating interactions between ER, AF1 and the AF2 coactivator complex by direct binding to these coactivators (65). The RNA helicase DDX3 and its role in c-MYC driven germinal center Debauve G, Capouillez A, Belayew A, Saussez S. Cell Mol Life Sci. Print 2021 May. Therefore, the demonstration that several DExD/H proteins interact with proteins that are known to be involved in the transcriptional regulation of genes involved in DNA repair and cell growth/cell cycle control have highlighted potentially important roles for DExD/H proteins in the development of cancer. doi: 10.1371/journal.pone.0200211. Functions in nucleotide excision repair; component of BTF2TFIIH transcription factor. Additionally, RHA has been shown to bind preferentially to the promoter sequence of the p16INK4a tumour suppressor gene in cells with transcriptionally active p16INK4a (28) and to be recruited to the promoter of the multidrug resistance gene (MDR1), upregulating transcription of the MDR1 gene (29). The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). They are motor proteins that bind ATP and then catalyze hydrolysis to release energy which is transduced for conformational changes. Ou Q., Mouillet J.F., Yan X., Dorn C., Crawford P.A., Sadovsky Y. Panel D, apoptotic cells (pyknotic fragmented nuclei, condensed and hypereosinophilic cytoplasm) in regions of encephalomalacia. p72 and its alternative translation initiation product p82 have themselves been shown to have RNA helicase activity in vitro (50,51) and p68 and p72 were subsequently shown to exist as heterodimers in cells (52). Several other reports have also suggested roles for RHA in cell cycle or growth regulation and cancer through its function in transcription. It is therefore tempting to speculate that p68, by virtue of its interactions with components of the transcriptional machinery (64,66) and with U1 snRNA at the 5 splice site (99), could act as a coupling factor between transcription and pre-mRNA processing. PDF Structural Basis for Helicase-Polymerase Coupling in the SARS-CoV-2 Before Bond A.T., Mangus D.A., He F., Jacobson A. Buszczak M., Spradling A.C. Interestingly, the interacting region for BRCA1 on RHA is separate from that for CBP implying that RHA also may interact specifically with other factors involved in transcription from specific promoters in response to particular signals. Human immunodeficiency virus type 1 (HIV-1) does not encode a helicase, thus it has to exploit cellular helicases in order to efficiently replicate its RNA genome. transcription - RNA polymerase and DNA helicase - Biology Stack Exchange Would you like email updates of new search results? An official website of the United States government. Bookshelf Controls (-antibody) and molecular size markers (bp) are provided for each experiment. The helicase-like transcription factor and its implication in cancer progression. J Photochem Photobiol B. No, you're not wrong. Gill G. Something about SUMO inhibits transcription. Deriving energy from ATP hydrolysis, helicases alter the structure of DNA, RNA, or DNA:RNA duplexes, remodeling chromatin and modulating access to the DNA template by the transcriptional machinery. Nuclear protein with sequence homology to translation initiation factor eIF-4A. Dual roles of RNA helicase A in CREB-dependent transcription. - Europe PMC RHA was found to interact both with the constitutive transport element (CTE) of simian type D retrovirus, being important for CTE-mediated nuclear export (30,31), and with the Rev response element (RRE) of HIV, stimulating both CTE- and Rev-dependent gene expression (32). The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor? The finding that p68 was one of the proteins co-purifying with spliceosomes in a mass spectrometric analysis of spliceosomal complexes (55) suggested a role for this protein in RNA splicing. Myohanen S., Baylin S.B. Integrating mRNA processing with transcription. Kwek K.Y., Murphy S., Furger A., Thomas B., O'Gorman W., Kimura H., Proudfoot N.J., Akoulitchev A. U1 snRNA associates with TFIIH and regulates transcriptional initiation. Ares M.Jr, Proudfoot N.J. 2016 Jan 13;80(1):139-60. doi: 10.1128/MMBR.00055-15. RHA has been found to fulfill a similar bridging role between the breast cancer-specific tumour suppressor BRCA1 and the Pol II holoenzyme, interacting with the transcriptionally active C-terminal domain BRCA1 (2022). The enzyme RNA polymerase binds to the template strand of DNA at the beginning of the sequence to be copied. The functions of these proteins are summarized in Table 1. Inclusion in an NLM database does not imply endorsement of, or agreement with, Lee C.G., Hurwitz J. Interestingly, RNA helicase-defective mutants of RHA showed a decreased ability to coactivate CBP-dependent transcription raising the possibility that, apart from being a bridging factor, RHA may enhance engagement of the transcriptional machinery at responsive promoters by inducing changes in chromatin structure through local DNA unwinding. Lee K., Pisarska M.D., Ko J.J., Kang Y., Yoon S., Ryou S.M., Cha K.Y., Bae J. Transcriptional factor FOXL2 interacts with DP103 and induces apoptosis. The DExD/H box family of proteins includes a large number of proteins that play important roles in RNA metabolism. The enigmatic helicase DHX9 and its association with the hallmarks of However the function of these proteins remained elusive, although the expression of p68 was shown to be growth and developmentally regulated and to correlate with organ maturation/differentiation (53), p72 appeared to be down-regulated during development (54). A bovine homologue of human RNA helicase A and Drosophila Mle protein. PCR amplification of DNA fragments from ChIP authenticated Hltf binding sites. (B) p68/p72 is known to interact with the AF1 domain of ER and p68 has been shown to interact with CBP and RNA Pol II, leading to the suggestion that p68/p72 may act as bridges between the ER AF1 domain and transcription factors interacting with the AF2 domain of ER. Federal government websites often end in .gov or .mil. The ATPase and/or helicase activity of RHA is required for CREB-dependent transcription. Roles of helicases in translation initiation: A mechanistic view H&E stained coronal sections from newborn Hltf null mouse brains (AD); caspase 3 assays comparing null and control brains (E); immunofluorescence image (F) and Western analysis of immunoprecipitates (G) from control brains. Sumoylation often correlates with transcriptional repression, which, at least in some cases, is mediated through HDAC recruitment (46). This would be consistent with several of these proteins being involved in cell growth and cell cycle regulation. Eferl R., Wagner E.F. AP-1: a double-edged sword in tumorigenesis. Another very interesting idea that emerges from these findings is that DExD/H proteins may be acting to couple processes such as transcription and RNA processing. 8600 Rockville Pike Ozgenc A., Loeb L.A. Current advances in unraveling the function of the Werner syndrome protein. Moreover, it has been suggested that the interaction of DP103 with the EpsteinBarr virus proteins EBNA2 and EBNA3C (37) may interfere with the METS/DP103 interaction and may contribute to transformation by this virus (44). Fairman M.E., Maroney P.A., Wang W., Bowers H.A., Gollnick P., Nilsen T.W., Jankowsky E. Protein displacement by DExH/D RNA helicases without duplex unwinding. General and Target-Specific DExD/H RNA Helicases in Eukaryotic Functional interaction between RNA helicase II/Gu(alpha) and ribosomal protein L4. In this review I shall concentrate on RNA helicase A (Dhx9), DP103 (Ddx20), p68 (Ddx5) and p72 (Ddx17), proteins for which there is a strong body of evidence showing that they play important roles in transcription, often as coactivators or corepressors through their interaction with key components of the transcriptional machinery, such as CREB . Colors for lines and symbols are green for positive, and gray for unspecified]. Of particular interest are the reports showing that some of these proteins, through interaction with components of the transcriptional machinery, play important roles in transcriptional regulation. Hence females have two active copies and males only . Prolonged exposure (10 minutes) of Western blots from control brain (lane 2) revealed faint evidence of a protein product from the truncated Hltf mRNA isoform 2. Warner D.R., Bhattacherjee V., Yin X., Singh S., Mukhopadhyay P., Pisano M.M., Greene R.M. This activity was subsequently found to be shared by p72 (65). However, mutants in both the transactivation domain and the ATP-binding motif exhibited reduced CREB-dependent transcriptional activity when co-transfected with plasmids encoding CBP and a CRE-luciferase reporter (19). Roles of accessory domains. The ATPase and/or helicase activity of RHA is required for CREB-dependent transcription. Disclaimer. The Ddx20/DP103 DEAD box protein represses transcriptional activation by Egr2/Krox-20. Exons are numbered green rectangles. DNA helicase is an enzyme that unwinds DNA to allow for replication. . Unlike replicative helicases, the DEAD and DExH box helicases involved in translation initiation cannot processively unwind long duplexes and appear to have a different mode of unwinding [41], [42], [43], [44].The helicase activity is mediated by binding to RNA in the presence of ATP, followed by cycles of ATP hydrolysis, release of the helicase from the RNA . Panel C, schematic of genotyping by PCR shows wild-type, floxed and knockout alleles with primer locations, and expected amplicon size. Stress responsive DEAD-box helicases: a new pathway to engineer plant stress tolerance. Therefore, the idea that RNA helicases, which might be required to unwind RNA in later stages of gene expression (e.g. This site needs JavaScript to work properly. Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells. Similarly RHII/Gu, through its coactivation of c-Jun transcriptional activity and promotion of c-Jun-mediated neuronal differentiation (74), could play a role in c-Jun mediated cell cycle regulation or apoptosis (94,95). Proudfoot N.J., Furger A., Dye M.J. This implies that p68 and p72, like RNA helicase A (17,20), may act as a bridge between transcription factors/coactivators, an idea that has been reinforced by other recent reports. In addition to Cap-H, Condensin I has two additional non-Smc subunits (Cap-D2 and Cap-G). PCR amplicons for each genotype are provided with DNA size markers. Hltf from full-length Hltf mRNA isoform 1 is shown in lane 1. Although BRCA1 is not itself a sequence-specific DNA-binding transcription factor, it has been shown to be involved in the transcriptional regulation of several genes involved in DNA repair, cell cycle and apoptosis (2325), presumably as a coregulator of transcription through its interactions with factors in the transcriptional machinery. Panel A, diagram showing the presence (wild-type) and absence. Thus RHA could be important in breast cancer development. Functional interaction between Smad, CREB binding protein, and p68 RNA helicase. Prokaryotic and eukaryotic DNA helicases - PMC - National Center for Colantoni A, Capauto D, Alfano V, D'Ambra E, D'Uva S, Tartaglia GG, Morlando M. Int J Mol Sci. J Mol Med (Berl). Lee C.G., Chang K.A., Kuroda M.I., Hurwitz J. For example, as discussed above, RHA has been shown to associate both with components of the transcriptional machinery and with the SMN complex in snRNPs (17,34), although it is unclear whether the pools of RHA molecules associating with transcription and spliceosome complexes are independent, or whether there is a transition from transcription- to spliceosome-associated RHA. Historically, most DExD/H box proteins have been associated with such cellular processes; indeed many members of this family were initially identified through investigations of mutants that led to specific defects in processes such as RNA processing, ribosome biogenesis and translation, and it is clear that the RNA unwinding activity of these proteins is essential for their function in such processes (9). The P element regulates odorant receptor choice. Scatter plot of expression level. Recent evidence suggests that helicase-domain-containing proteins are also involved in complexes that facilitate the activity of groups of seemingly unrelated genes. official website and that any information you provide is encrypted Bethesda, MD 20894, Web Policies Microbiol Mol Biol Rev. Careers, Unable to load your collection due to an error. eCollection 2018. Their prominence is marked by various cancers and genetic disorders that are linked to helicase defects. Dual Roles of RNA Helicase A in CREB-Dependent Transcription PMC Dual roles of RNA helicase A in CREB-dependent transcription Ishizuka A., Siomi M.C., Siomi H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. MLE activates transcription via the minimal transactivation domain in Drosophila. Furthermore, it has been known for a long time that the positioning of the first intron and its 5 splice site have a profound effect on transcription efficiency in transgenic mouse models (102,103). The enzyme DNA helicase breaks the hydrogen bonds between the bases in a specific region of the DNA molecule. PMC In transcription termination, the hairpin causes the RNA polymerase to stall and the transcript to separate from the DNA. Role of Helicase-Like Transcription Factor (Hltf) in the G2/M Many of the studies that have demonstrated roles for these proteins in transcription have shown that they function through interaction with transcriptional coactivators/corepressors. Staley J.P., Guthrie C. Mechanical devices of the spliceosome: motors, clocks, springs and things. Panel B, schematic of the Hltf wild-type, floxed, and knockout alleles with restriction sites for the 3-Southern blot strategy. Accessibility Some examples are discussed below. RNA-dependent association of the, Lee C.G., Hurwitz J. Schwer B. For ER, although the interacting region between p68/p72 and ER included part of the conserved helicase core and RNA binding was important for ER coactivation, p68 helicase activity per se was not required (64,65). Lamm G.M., Nicol S.M., Fuller-Pace F.V., Lamond A.I. Wei X., Pacyna-Gengelbach M., Schluns K., An Q., Gao Y., Cheng S., Petersen I. Helicases have major roles in genome maintenance by unwinding structured nucleic acids. DNA helicases, known for their fundamentally important roles in genomic stability, are high profile players in cancer. DNA helicases involved in DNA repair and their roles in cancer The finding that p68 coactivated ER function (64) not only demonstrated for the first time a role for p68 in transcriptional regulation but also highlighted a potential link with tumour development. A recent report has demonstrated that p68 acts as a potent coactivator for the tumour suppressor p53, a latent transcription factor that is induced and activated in response to stresses, such as DNA damage, and induces transcription of genes involved in cell cycle arrest and apoptosis. DExH-Box helicase 9 (DHX9), also known as RNA helicase A (RHA), belongs to the DExD/H-Box superfamily II of helicases [ 1 ]. RNA helicase A interacts with dsDNA and topoisomerase II. Hartman T.R., Qian S., Bolinger C., Fernandez S., Schoenberg D.R., Boris-Lawrie K. RNA helicase A is necessary for translation of selected messenger RNAs. Lee C.G., Reichman T.W., Baik T., Mathews M.B. The human RNA helicase A (DDX9) gene maps to the prostate cancer susceptibility locus at chromosome band 1q25 and its pseudogene (DDX9P) to 13q22, respectively. Metivier R., Penot G., Hubner M.R., Reid G., Brand H., Kos M., Gannon F. Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. These findings thus suggest that the activity of p68/72 in transcriptional regulation is distinct from their activity in RNA processing and supports the idea that they are truly multifunctional proteins with roles in several cellular processes. Alternative splicing of helicase-like transcription factor (Hltf): Intron retention-dependent activation of immune tolerance at the feto-maternal interface. Conflict of interest statement. The picture now emerging on the function of many DExD/H proteins is considerably more complicated than their acting simply as motors to unwind RNA or displace proteins from RNA. Guil S., Gattoni R., Carrascal M., Abian J., Stevenin J., Bach-Elias M. Roles of hnRNP A1, SR proteins, and p68 helicase in c-H-ras alternative splicing regulation. Hltf null brains have reduced transcript levels for Rad21/Scc1, histone H3.3, Cap-E/Smc2, Cap-G/G2, and Aurora B kinase. DExD/H proteins have long been known to function as part of large RNP complexes in processes such as pre-mRNA processing, translation initiation and ribosome assembly (2). Introns increase transcriptional efficiency in transgenic mice. splicing), are also functioning as part of the transcription machinery (perhaps in an RNA helicase-independent manner), to facilitate mature mRNA production, is very exciting. Federal government websites often end in .gov or .mil. Cohesin/condensin contain structural maintenance of, Figure 7. However, it is clear that several members of this family are multifunctional and, in addition to acting as RNA helicases in processes such as pre-mRNA processing, play important roles in transcriptional regulation. MeSH Rowell S., Newman B., Boyd J., King M.C. The DEAD-Box RNA Helicase DDX3 Interacts with NF-B Subunit p65 - PLOS Panel B, higher magnification of the cholinergic-rich ventral paladium involved in regulation of motivation and behavior. Regulation of alternative splicing by the ATP-dependent DEAD-box RNA helicase p72. In recent years, however, most of the reports on DP103 have concentrated on its role in transcription and have provided more direct evidence for its role as a transcriptional regulator. The ZBD is in close proximity to ribosome in the RNAP-ribosome complexes, suggesting its roles in regulating the transcription-translation coupling. Moreover, it reveals how silencing Hltf disrupts cell cycle progression, and attenuates DNA damage repair. 2016 Jan;73(1):129-47. doi: 10.1007/s00018-015-2060-6. Godbout R., Packer M., Bie W. Overexpression of a DEAD box protein (DDX1) in neuroblastoma and retinoblastoma cell lines. The DEAD-box protein DP103 (Ddx20 or Gemin-3) represses orphan nuclear receptor activity via SUMO modification. Abstract - DNA helicases are enzymes that are able to unwind DNA by the use of the energy-equivalent ATP. 2B The C-terminal domain of DP103 was again demonstrated to have intrinsic transcriptional repression activity and to be required for the METS-dependent block in cell proliferation. official website and that any information you provide is encrypted Hltf also regulates Smad7/Bambi/Tgf-beta/Bmp5/Wnt10b signaling in brain. Here, we review the roles of topoisomerases in mediating chromatin dynamics, transcription, replication, DNA damage repair and genomic stability, and discuss how deregulation of topoisomerases. At the end of the multistep transcription process, the elongating RNA polymerase (RNAP) is dislodged from the DNA template either at specific DNA sequences, called the terminators, or by a nascent RNA-dependent helicase, Rho. Detection of a novel ATP-dependent cross-linked protein at the 5 splice site-U1 small nuclear RNA duplex by methylene blue-mediated photo-cross-linking. Second, it was found to interact with Smad3 [a member of the Smad family of transcriptional activators that act as intracellular effectors of TGF- (67)] and to form part of a ternary complex with Smad3 and CBP (68). Activation of gene expression by ER is mediated by two autonomous transcription activation domains, AF1 and AF2. Figure 5. and transmitted securely. Unraveling the role of helicases in transcription - PubMed Accessibility The association of the N- and C-termini of Smc1 and Smc3 with Rad21/Scc1, a kleisin family member that controls separation of sister-chromatids, completes the tripartite ring-like structure.
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