Genomes and Genes
nuclear factor 90 proteins
Summary: A family of double-stranded RNA-binding proteins that are related to NFATC TRANSCRIPTION FACTORS. In addition to binding to RNA, nuclear factor 90 proteins form heterodimeric complexes that regulate GENETIC TRANSCRIPTION and may play a role in T-CELL activation.
- Marcoulatos P, Koussidis G, Mamuris Z, Velissariou V, Vamvakopoulos N. Mapping interleukin enhancer binding factor 2 gene (ILF2) to human chromosome 1 (1q11-qter and 1p11-p12) by polymerase chain reaction amplification of human-rodent somatic cell hybrid DNA templates. J Interferon Cytokine Res. 1996;16:1035-8 pubmed
- Nie Y, Ding L, Kao P, Braun R, Yang J. ADAR1 interacts with NF90 through double-stranded RNA and regulates NF90-mediated gene expression independently of RNA editing. Mol Cell Biol. 2005;25:6956-63 pubmed..These data suggest that ADAR1 has the potential both to change information content through editing of mRNA and to regulate gene expression through interacting with the NF90 family proteins. ..
- Shim J, Lim H, R Yates J, Karin M. Nuclear export of NF90 is required for interleukin-2 mRNA stabilization. Mol Cell. 2002;10:1331-44 pubmed..In nonstimulated cells, NF90 is mostly nuclear, but T cell activation results in its accumulation in the cytoplasm. The nuclear export of NF90 is required for IL-2 mRNA stabilization. ..
- Shin H, Kim S, Cho Y, Lee S, Rho H. Host cell proteins binding to the encapsidation signal epsilon in hepatitis B virus RNA. Arch Virol. 2002;147:471-91 pubmed..Previously, we also proposed that the GRP94 was associated with HBV polymerase in the human liver cell HepG2. These results suggest that the heterodimeric factor plays an important role in the priming activity of HBV polymerase. ..
- Guan D, Altan Bonnet N, Parrott A, ARRIGO C, Li Q, Khaleduzzaman M, et al. Nuclear factor 45 (NF45) is a regulatory subunit of complexes with NF90/110 involved in mitotic control. Mol Cell Biol. 2008;28:4629-41 pubmed publisher..Furthermore, the study revealed that NF90 is functionally distinct from NF110 and is more important for cell growth. ..
- Kuwano Y, Kim H, Abdelmohsen K, Pullmann R, Martindale J, Yang X, et al. MKP-1 mRNA stabilization and translational control by RNA-binding proteins HuR and NF90. Mol Cell Biol. 2008;28:4562-75 pubmed publisher..Collectively, MKP-1 upregulation by oxidative stress is potently influenced by increased mRNA stability and translation, mediated at least in part by the RNA-BPs HuR and NF90. ..
- Kiesler P, Haynes P, Shi L, Kao P, Wysocki V, Vercelli D. NF45 and NF90 regulate HS4-dependent interleukin-13 transcription in T cells. J Biol Chem. 2010;285:8256-67 pubmed publisher..Collectively, our results identify NF45 and NF90 as novel regulators of HS4-dependent human IL13 transcription in response to T cell activation. ..
- Harashima A, Guettouche T, Barber G. Phosphorylation of the NFAR proteins by the dsRNA-dependent protein kinase PKR constitutes a novel mechanism of translational regulation and cellular defense. Genes Dev. 2010;24:2640-53 pubmed publisher..Thus, the NFARs constitute a novel, conserved mechanism of host defense used by the cell to detect and impede aberrant translation events. ..
- Smith N, Miskimins W. Phosphorylation at serine 482 affects stability of NF90 and its functional role in mitosis. Cell Prolif. 2011;44:147-55 pubmed publisher..Based on the sequence surrounding S482, mitotic kinase PLK1 is a strong candidate for the enzyme that phosphorylates NF90 at this site. ..
- Patel R, Vestal D, Xu Z, Bandyopadhyay S, Guo W, Erme S, et al. DRBP76, a double-stranded RNA-binding nuclear protein, is phosphorylated by the interferon-induced protein kinase, PKR. J Biol Chem. 1999;274:20432-7 pubmed..Finally, purified DRBP76 was shown to be a substrate of PKR in vitro, indicating that this protein's cellular activities may be regulated by PKR-mediated phosphorylation. ..
- Ohno M, Komakine J, Suzuki E, Nishizuka M, Osada S, Imagawa M. Interleukin enhancer-binding factor 3 functions as a liver receptor homologue-1 co-activator in synergy with the nuclear receptor co-activators PRMT1 and PGC-1?. Biochem J. 2011;437:531-40 pubmed publisher..Taken together, our results suggest that ILF3 functions as a novel LRH-1 co-activator by acting synergistically with PRMT1 and PGC-1?, thereby promoting LRH-1-dependent gene expression. ..
- Langland J, Kao P, Jacobs B. Nuclear factor-90 of activated T-cells: A double-stranded RNA-binding protein and substrate for the double-stranded RNA-dependent protein kinase, PKR. Biochemistry. 1999;38:6361-8 pubmed..The NF90 protein was found to be expressed not only in T-cells, but also in nonimmune HeLa cells. In HeLa cells, the protein was almost exclusively localized to the ribosome salt wash fraction of cell lysates. ..
- Shamanna R, Hoque M, Lewis Antes A, Azzam E, Lagunoff D, PE ERY T, et al. The NF90/NF45 complex participates in DNA break repair via nonhomologous end joining. Mol Cell Biol. 2011;31:4832-43 pubmed publisher..Further, NF90/NF45 knockdown reduced end-joining activity in vivo. These results identify the NF90/NF45 complex as a regulator of DNA damage repair mediated by DNA-PK and suggest that structured RNA may modulate this process. ..
- GOMILA R, Martin G, Gehrke L. NF90 binds the dengue virus RNA 3' terminus and is a positive regulator of dengue virus replication. PLoS ONE. 2011;6:e16687 pubmed publisher..NF90 depletion diminished the production of infectious dengue virus by more than 50%, which may have important significance for identifying therapeutic targets to limit a virus that threatens more than a billion people worldwide. ..
- Sakamoto S, Aoki K, Higuchi T, Todaka H, Morisawa K, Tamaki N, et al. The NF90-NF45 complex functions as a negative regulator in the microRNA processing pathway. Mol Cell Biol. 2009;29:3754-69 pubmed publisher..These findings suggest that the association of the NF90-NF45 complex with pri-miRNAs impairs access of the Microprocessor complex to the pri-miRNAs, resulting in a reduction of mature miRNA production. ..
- ..Knock-down or over-expression of these genes suggested that hnRNPR inhibits, whereas hnRNPH1 facilitates, miRNA processing. Overall, our results emphasize that miRNA biogenesis is versatile. ..
- Viranaicken W, Gasmi L, Chauvin C, Denoulet P, Larcher J. Identification of a newly spliced exon in the mouse Ilf3 gene generating two long and short isoforms of Ilf3 and NF90. Genomics. 2006;88:622-32 pubmed..By RT-PCR, no other variants were found. Combining our results and GenBank sequences, we determined the exon-intron organization of the entire mouse Ilf3 gene divided into 22 exons. ..
- Yang F, Huo X, Yuan S, Zhang L, Zhou W, Wang F, et al. Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell. 2013;49:1083-96 pubmed publisher..These results advance our understanding of the role of lncRNA-LET as a regulator of hypoxia signaling and offer new avenues for therapeutic intervention against cancer progression. ..
- Parrott A, Walsh M, Reichman T, Mathews M. RNA binding and phosphorylation determine the intracellular distribution of nuclear factors 90 and 110. J Mol Biol. 2005;348:281-93 pubmed..We conclude that NF90 and NF110 engage RNA differentially and translocate from the nucleus to the cytoplasm in mitosis because phosphorylation disturbs their interactions with other nuclear proteins. ..
- Larcher J, Gasmi L, Viranaicken W, Edde B, Bernard R, Ginzburg I, et al. Ilf3 and NF90 associate with the axonal targeting element of Tau mRNA. FASEB J. 2004;18:1761-3 pubmed..This observation favors the idea that Ilf3 and NF90 are part of a protein complex that escorts Tau mRNA toward the axon. ..
- Reichman T, Parrott A, Fierro Monti I, Caron D, Kao P, Lee C, et al. Selective regulation of gene expression by nuclear factor 110, a member of the NF90 family of double-stranded RNA-binding proteins. J Mol Biol. 2003;332:85-98 pubmed..Finally, we demonstrate that NF110b associates with the dsRBM-containing transcriptional co-activator, RNA helicase A, independently of RNA binding. ..
- Rezai Zadeh N, Zhang X, Namour F, Fejer G, Wen Y, Yao Y, et al. Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1. Genes Dev. 2003;17:1019-29 pubmed..Our data confirm that histone methylation does not occur randomly but rather is a targeted event and provides one mechanism by which HMTs can be recruited to chromatin to activate gene expression. ..
- Brownawell A, Macara I. Exportin-5, a novel karyopherin, mediates nuclear export of double-stranded RNA binding proteins. J Cell Biol. 2002;156:53-64 pubmed..We propose that exportin-5 is not an RNA export factor but instead participates in the regulated translocation of dsRBD proteins to the cytoplasm where they interact with target mRNAs. ..
- Krasnoselskaya Riz I, Spruill A, Chen Y, Schuster D, Teslovich T, Baker C, et al. Nuclear factor 90 mediates activation of the cellular antiviral expression cascade. AIDS Res Hum Retroviruses. 2002;18:591-604 pubmed..This leads to a hypothesis as to the mechanism of action of NF90 in mediating endogenous antiviral responses. ..
- Shabman R, Leung D, Johnson J, Glennon N, Gulcicek E, Stone K, et al. DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function. J Infect Dis. 2011;204 Suppl 3:S911-8 pubmed publisher..These data suggest that DRBP76, via its association with VP35, exerts an anti-EBOV function. ..
- Guo Y, Fu P, Zhu H, Reed E, Remick S, Petros W, et al. Correlations among ERCC1, XPB, UBE2I, EGF, TAL2 and ILF3 revealed by gene signatures of histological subtypes of patients with epithelial ovarian cancer. Oncol Rep. 2012;27:286-92 pubmed publisher..Further investigation of these genes may enable better understanding of the molecular mechanism of tumorigenesis and identification of potential biomarkers. ..
- Langland J, Kao P, Jacobs B. Regulation of IL-2 gene expression and nuclear factor-90 translocation in vaccinia virus-infected cells. J Interferon Cytokine Res. 2003;23:489-500 pubmed..Other VV mutants that produced excess dsRNA also inhibited protein binding to the IL-2 enhancer, suggesting that the presence of viral dsRNA has a role in retaining NF-90 in the cytosol and regulating IL-2 gene expression. ..
- Corso C, Pisapia L, Citro A, Cicatiello V, Barba P, Cigliano L, et al. EBP1 and DRBP76/NF90 binding proteins are included in the major histocompatibility complex class II RNA operon. Nucleic Acids Res. 2011;39:7263-75 pubmed publisher..We propose that the concept of 'RNA operon' may be suitable for our system in which MHCII mRNAs are modulated via interaction of their 3'UTR with same proteins. ..
- Reichman T, Mathews M. RNA binding and intramolecular interactions modulate the regulation of gene expression by nuclear factor 110. RNA. 2003;9:543-54 pubmed..We propose a model in which structured RNAs regulate gene expression by modulating transcription through interactions with members of the NF90 protein family. ..
- Xu Y, Grabowski G. Molecular cloning and characterization of a translational inhibitory protein that binds to coding sequences of human acid beta-glucosidase and other mRNAs. Mol Genet Metab. 1999;68:441-54 pubmed..TCP80 is likely identical to MPP4 and NF90, but has previously undescribed roles in cellular function. ..
- Saunders L, Perkins D, Balachandran S, Michaels R, Ford R, Mayeda A, et al. Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR. J Biol Chem. 2001;276:32300-12 pubmed..Collectively, our data indicate that the NFARs may facilitate double-stranded RNA-regulated gene expression at the level of post-transcription and possibly contribute to host defense-related mechanisms in the cell. ..
- Isken O, Grassmann C, Sarisky R, Kann M, Zhang S, Grosse F, et al. Members of the NF90/NFAR protein group are involved in the life cycle of a positive-strand RNA virus. EMBO J. 2003;22:5655-65 pubmed..Because NFAR proteins are presumed components of the antiviral response, we suspect that viral recruitment may also serve to weaken cellular defense mechanisms. ..
- Hoque M, Shamanna R, Guan D, PE ERY T, Mathews M. HIV-1 replication and latency are regulated by translational control of cyclin T1. J Mol Biol. 2011;410:917-32 pubmed publisher..This investigation reveals a novel mechanism of cyclin T1 regulation and establishes NF90 as a regulator of HIV-1 replication during both productive infection and induction from latency. ..
- Reichman T, Muniz L, Mathews M. The RNA binding protein nuclear factor 90 functions as both a positive and negative regulator of gene expression in mammalian cells. Mol Cell Biol. 2002;22:343-56 pubmed..This report characterizes NF90 as both a positive and negative regulator of gene expression, depending on the promoter context, and suggests a role for NF45 as a regulator of NF90. ..
- Gwizdek C, Ossareh Nazari B, Brownawell A, Evers S, Macara I, Dargemont C. Minihelix-containing RNAs mediate exportin-5-dependent nuclear export of the double-stranded RNA-binding protein ILF3. J Biol Chem. 2004;279:884-91 pubmed..Exportin-5 thus appears as the first example of a nuclear export receptor that mediates RNA export but also promotes transport of proteinaceous cargo through appropriate and specific RNA adaptors. ..
- Bose S, Sengupta T, Bandyopadhyay S, Spicer E. Identification of Ebp1 as a component of cytoplasmic bcl-2 mRNP (messenger ribonucleoprotein particle) complexes. Biochem J. 2006;396:99-107 pubmed..Collectively, these results indicate a novel function for Ebp1 in contributing to the regulation of bcl-2 expression in HL-60 cells. ..
- Urcuqui Inchima S, Castaño M, Hernandez Verdun D, St Laurent G, Kumar A. Nuclear Factor 90, a cellular dsRNA binding protein inhibits the HIV Rev-export function. Retrovirology. 2006;3:83 pubmed..Our results are consistent with a model of Rev-mediated HIV-1 RNA export that envisions Rev-multimerization, a process interrupted by NF90ctv. ..
- Ulke Lemee A, Trinkle Mulcahy L, Chaulk S, Bernstein N, Morrice N, Glover M, et al. The nuclear PP1 interacting protein ZAP3 (ZAP) is a putative nucleoside kinase that complexes with SAM68, CIA, NF110/45, and HNRNP-G. Biochim Biophys Acta. 2007;1774:1339-50 pubmed..In ZAP3, although this domain is present, it now appears degenerate and functions to bind PP1 through an RVRW docking site located within the domain. ..
- Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N. Nucleolar localization of DGCR8 and identification of eleven DGCR8-associated proteins. Exp Cell Res. 2007;313:4196-207 pubmed..Thus, our studies provided additional new evidence for the involvement of various protein complexes in the molecular mechanisms of apparently complex innate RNA interference machinery. ..
- Agbottah E, Traviss C, McArdle J, Karki S, St Laurent G, Kumar A. Nuclear Factor 90(NF90) targeted to TAR RNA inhibits transcriptional activation of HIV-1. Retrovirology. 2007;4:41 pubmed..Structural integrity of the TAR element is crucial in HIV-1 gene expression. Our results show that perturbation Tat/TAR RNA interaction by the dsRNA binding protein is sufficient to inhibit transcriptional activation of HIV-1. ..
- Marcoulatos P, Avgerinos E, Tsantzalos D, Vamvakopoulos N. Mapping interleukin enhancer binding factor 3 gene (ILF3) to human chromosome 19 (19q11-qter and 19p11-p13.1) by polymerase chain reaction amplification of human-rodent somatic cell hybrid DNA templates. J Interferon Cytokine Res. 1998;18:351-5 pubmed..1) by polymerase chain reaction (PCR) amplification of ILF3-specific DNA sequences from well-characterized human-rodent somatic cell hybrid DNAs. ..
- Buaas F, Lee K, Edelhoff S, Disteche C, Braun R. Cloning and characterization of the mouse interleukin enhancer binding factor 3 (Ilf3) homolog in a screen for RNA binding proteins. Mamm Genome. 1999;10:451-6 pubmed
- Zhu P, Jiang W, Cao L, Yu W, Pei Y, Yang X, et al. IL-2 mRNA stabilization upon PMA stimulation is dependent on NF90-Ser647 phosphorylation by protein kinase CbetaI. J Immunol. 2010;185:5140-9 pubmed publisher..Thus, our study elucidates the mechanism by which PMA activates and stabilizes IL-2 expression in T cells. ..
- Vumbaca F, Phoenix K, Rodriguez Pinto D, Han D, Claffey K. Double-stranded RNA-binding protein regulates vascular endothelial growth factor mRNA stability, translation, and breast cancer angiogenesis. Mol Cell Biol. 2008;28:772-83 pubmed..These data demonstrate that the DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading onto polysomes and translation under hypoxic conditions, thus promoting breast cancer growth and angiogenesis in vivo. ..
- Xu Y, Leonova T, Grabowski G. Cell cycle dependent intracellular distribution of two spliced isoforms of TCP/ILF3 proteins. Mol Genet Metab. 2003;80:426-36 pubmed..This study indicates that the multiple cellular functions, i.e., translation control, interleukin-2 enhancer binding, or cell division, of TCP/ILF3 are fulfilled by alternatively spliced isoforms. ..
- Tran H, Schilling M, Wirbelauer C, Hess D, Nagamine Y. Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU. Mol Cell. 2004;13:101-11 pubmed..ARE(uPA)-mRNA recognition by RHAU may be mediated through its RNA-dependent interaction with the AUBPs HuR and NFAR1. A model is presented to describe the action of RHAU in ARE(uPA)-directed mRNA turnover. ..
- Aoki Y, Zhao G, Qiu D, Shi L, Kao P. CsA-sensitive purine-box transcriptional regulator in bronchial epithelial cells contains NF45, NF90, and Ku. Am J Physiol. 1998;275:L1164-72 pubmed..Antibodies to Ku potently inhibit the purine-box DNA-binding complex. The purine-box transcriptional regulator in 16HBE cells likely comprises NF45, NF90, Ku80, Ku70, and the DNA-dependent protein kinase catalytic subunit. ..
- Neplioueva V, Dobrikova E, Mukherjee N, Keene J, Gromeier M. Tissue type-specific expression of the dsRNA-binding protein 76 and genome-wide elucidation of its target mRNAs. PLoS ONE. 2010;5:e11710 pubmed publisher..Thus, the functional role of DRBP76 in co- or post-transcriptional gene regulation may contribute to the neoplastic phenotype. ..
- Shi L, Godfrey W, Lin J, Zhao G, Kao P. NF90 regulates inducible IL-2 gene expression in T cells. J Exp Med. 2007;204:971-7 pubmed..Thus, NF90 regulates inducible IL-2 transcription, mRNA stability, and gene expression in T cells and represents a novel therapeutic target for the modulation of T cell immune responses. ..
- Saunders L, Jurecic V, Barber G. The 90- and 110-kDa human NFAR proteins are translated from two differentially spliced mRNAs encoded on chromosome 19p13. Genomics. 2001;71:256-9 pubmed..Our studies, the first to elucidate the gene structure and chromosomal assignment of NFAR, establish the genetic basis for future NFAR research in humans. ..
- Tang J, Kao P, Herschman H. Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3. J Biol Chem. 2000;275:19866-76 pubmed..Because of this difference, NF90 does not interact with PRMT1, is a much poorer substrate than ILF3 for PRMT1-dependent methylation, and does not modulate PRMT1 enzyme activity. ..
- Kuwano Y, Pullmann R, Marasa B, Abdelmohsen K, Lee E, Yang X, et al. NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif. Nucleic Acids Res. 2010;38:225-38 pubmed publisher..In summary, we have identified an AU-rich RNA motif present in NF90 target mRNAs and have obtained evidence that NF90 represses the translation of this subset of mRNAs. ..
- Chen T, Brownawell A, Macara I. Nucleocytoplasmic shuttling of JAZ, a new cargo protein for exportin-5. Mol Cell Biol. 2004;24:6608-19 pubmed..Together, these data suggest that JAZ is exported by exportin-5 but translocates back into nuclei by a facilitated diffusion mechanism. ..
- Parker L, Fierro Monti I, Mathews M. Nuclear factor 90 is a substrate and regulator of the eukaryotic initiation factor 2 kinase double-stranded RNA-activated protein kinase. J Biol Chem. 2001;276:32522-30 pubmed..The C-terminal region also inhibits PKR function, probably through competitive binding to dsRNA. A model for NF90-PKR interactions is proposed. ..
- Cazanove O, Batut J, Scarlett G, Mumford K, Elgar S, Thresh S, et al. Methylation of Xilf3 by Xprmt1b alters its DNA, but not RNA, binding activity. Biochemistry. 2008;47:8350-7 pubmed publisher..Several other proteins involved in gene regulation can bind both RNA and DNA; these data demonstrate a mechanism by which such binding activities may be controlled independently. ..
- Pei Y, Zhu P, Dang Y, Wu J, Yang X, Wan B, et al. Nuclear export of NF90 to stabilize IL-2 mRNA is mediated by AKT-dependent phosphorylation at Ser647 in response to CD28 costimulation. J Immunol. 2008;180:222-9 pubmed..In vivo and in vitro data support a model in which CD28 costimulation activates AKT to phosphorylate NF90 at Ser647 and phosphorylation triggers NF90 to relocate to the cytoplasm and stabilize IL-2 mRNA. ..
- Ranpura S, Deshmukh U, Reddi P. NF45 and NF90 in murine seminiferous epithelium: potential role in SP-10 gene transcription. J Androl. 2008;29:186-97 pubmed..Based on these results, we propose that NF45 and NF90 have the potential to activate SP-10 gene transcription, and that a chromatin modification event must occur first in order to provide access to these transcription factors...
- Kao P, Chen L, Brock G, Ng J, Kenny J, Smith A, et al. Cloning and expression of cyclosporin A- and FK506-sensitive nuclear factor of activated T-cells: NF45 and NF90. J Biol Chem. 1994;269:20691-9 pubmed
- Karmakar S, Mahajan M, Schulz V, Boyapaty G, Weissman S. A multiprotein complex necessary for both transcription and DNA replication at the ?-globin locus. EMBO J. 2010;29:3260-71 pubmed publisher..These results imply a direct link between mammalian DNA replication, transcription and histone acetylation mediated by a single multiprotein complex. ..