Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs - PubMed (original) (raw)
Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs
S H Ou et al. J Virol. 1995 Jun.
Abstract
Human immunodeficiency virus type 1 (HIV-1) gene expression is modulated by both viral and cellular factors. A regulatory element in the HIV-1 long terminal repeat known as TAR, which extends from nucleotides -18 to +80, is critical for the activation of gene expression by the transactivator protein, Tat. RNA transcribed from TAR forms a stable stem-loop structure which serves as the binding site for both Tat and cellular factors. Although TAR RNA is critical for Tat activation, the role that TAR DNA plays in regulating HIV-1 gene expression is not clear. Several studies have demonstrated that TAR DNA can bind cellular proteins, such as UBP-1/LBP-1, which repress HIV-1 gene expression and other factors which are involved in the generation of short, nonprocessive transcripts. In an attempt to characterize additional cellular factors that bind to TAR DNA, a lambda gt11 expression cloning strategy involving the use of a portion of TAR DNA extending from -18 to +28 to probe a HeLa cDNA library was used. We identified a cDNA, designated TAR DNA-binding protein (TDP-43), which encodes a cellular factor of 43 kDa that binds specifically to pyrimidine-rich motifs in TAR. Antibody to TDP-43 was used in gel retardation assays to demonstrate that endogenous TDP-43, present in HeLa nuclear extract, also bound to TAR DNA. Although TDP-43 bound strongly to double-stranded TAR DNA via its ribonucleoprotein protein-binding motifs, it did not bind to TAR RNA extending from +1 to +80. To determine the function of TDP-43 in regulating HIV-1 gene expression, in vitro transcription analysis was performed. TDP-43 repressed in vitro transcription from the HIV-1 long terminal repeat in both the presence and absence of Tat, but it did not repress transcription from other promoters such as the adenovirus major late promoter. In addition, transfection of a vector which expressed TDP-43 resulted in the repression of gene expression from an HIV-1 provirus. These results indicate that TDP-43 is capable of modulating both in vitro and in vivo HIV-1 gene expression by either altering or blocking the assembly of transcription complexes that are capable of responding to Tat.
Similar articles
- tat regulates binding of the human immunodeficiency virus trans-activating region RNA loop-binding protein TRP-185.
Wu F, Garcia J, Sigman D, Gaynor R. Wu F, et al. Genes Dev. 1991 Nov;5(11):2128-40. doi: 10.1101/gad.5.11.2128. Genes Dev. 1991. PMID: 1936997 - Tat functions to stimulate the elongation properties of transcription complexes paused by the duplicated TAR RNA element of human immunodeficiency virus 2.
García-Martínez LF, Mavankal G, Peters P, Wu-Baer F, Gaynor RB. García-Martínez LF, et al. J Mol Biol. 1995 Dec 1;254(3):350-63. doi: 10.1006/jmbi.1995.0622. J Mol Biol. 1995. PMID: 7490754 - Human immunodeficiency virus type 1 TAR element revertant viruses define RNA structures required for efficient viral gene expression and replication.
Harrich D, Mavankal G, Mette-Snider A, Gaynor RB. Harrich D, et al. J Virol. 1995 Aug;69(8):4906-13. doi: 10.1128/JVI.69.8.4906-4913.1995. J Virol. 1995. PMID: 7609059 Free PMC article. - Tackling Tat.
Karn J. Karn J. J Mol Biol. 1999 Oct 22;293(2):235-54. doi: 10.1006/jmbi.1999.3060. J Mol Biol. 1999. PMID: 10550206 Review. - Activation of HIV-1 transcription by Tat in cells derived from the CNS: evidence for the participation of NF-kappa B--a review.
Taylor JP, Khalili K. Taylor JP, et al. Adv Neuroimmunol. 1994;4(3):291-303. doi: 10.1016/s0960-5428(06)80270-6. Adv Neuroimmunol. 1994. PMID: 7874398 Review.
Cited by
- Conformational Enigma of TDP-43 Misfolding in Neurodegenerative Disorders.
Pillai M, Jha SK. Pillai M, et al. ACS Omega. 2024 Sep 20;9(39):40286-40297. doi: 10.1021/acsomega.4c04119. eCollection 2024 Oct 1. ACS Omega. 2024. PMID: 39372031 Free PMC article. Review. - HIV-1 Vpu induces neurotoxicity by promoting Caspase 3-dependent cleavage of TDP-43.
Yang J, Li Y, Li H, Zhang H, Guo H, Zheng X, Yu XF, Wei W. Yang J, et al. EMBO Rep. 2024 Oct;25(10):4337-4357. doi: 10.1038/s44319-024-00238-y. Epub 2024 Sep 6. EMBO Rep. 2024. PMID: 39242776 Free PMC article. - The prion-like effect and prion-like protein targeting strategy in amyotrophic lateral sclerosis.
Wenzhi Y, Xiangyi L, Dongsheng F. Wenzhi Y, et al. Heliyon. 2024 Jul 22;10(15):e34963. doi: 10.1016/j.heliyon.2024.e34963. eCollection 2024 Aug 15. Heliyon. 2024. PMID: 39170125 Free PMC article. Review. - Downregulation of miRNA-26a by HIV-1 Enhances CD59 Expression and Packaging, Impacting Virus Susceptibility to Antibody-Dependent Complement-Mediated Lysis.
Bellini N, Ye C, Ajibola O, Murooka TT, Lodge R, Cohen ÉA. Bellini N, et al. Viruses. 2024 Jul 4;16(7):1076. doi: 10.3390/v16071076. Viruses. 2024. PMID: 39066239 Free PMC article. - Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS.
Min JH, Sarlus H, Harris RA. Min JH, et al. Front Mol Neurosci. 2024 Jul 9;17:1408159. doi: 10.3389/fnmol.2024.1408159. eCollection 2024. Front Mol Neurosci. 2024. PMID: 39050823 Free PMC article. Review.
References
- Cell. 1989 Oct 20;59(2):273-82 - PubMed
- Cell. 1989 Oct 20;59(2):283-92 - PubMed
- Science. 1990 Mar 9;247(4947):1216-9 - PubMed
- EMBO J. 1990 Aug;9(8):2537-42 - PubMed
- Cell. 1990 Aug 24;62(4):757-67 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous