Trans-activation response element (TAR)

The HIV trans-activation response (TAR) element is an RNA element which is known to be required for the trans-activation of the viral promoter and for virus replication. The TAR hairpin is a dynamic structure[1] that acts as a binding site for the Tat protein, and this interaction stimulates the activity of the long terminal repeat promoter.[2]

Trans-activation response element (TAR)
Predicted secondary structure and sequence conservation of mir-TAR
Identifiers
Symbolmir-TAR
Alt. SymbolsTAR
RfamRF00250
Other data
RNA typeGene; miRNA
Domain(s)Viruses
GOGO:0035068 GO:0035195
SOSO:0000233 SO:0001244
PDB structuresPDBe

Further analysis has shown that TAR is a pre-microRNA that produces mature microRNAs from both strands of the TAR stem-loop.[3] These miRNAs are thought to prevent infected cells from undergoing apoptosis by downregulating the genes ERCC1, IER3,[4] CDK9, and Bim.[5]

Human polyomavirus 2 (JC virus) contains a TAR-homologous sequence in its late promoter[6] that is responsive to HIV-1 derived Tat.[7][8]

References
  1. Lu, Jia; Kadakkuzha, Beena M.; Zhao, Liang; et al. (2011). "Dynamic Ensemble View of the Conformational Landscape of HIV-1 TAR RNA and Allosteric Recognition". Biochemistry. 50 (22): 5042–5057. doi:10.1021/bi200495d. PMID 21553929.
  2. Kulinski, T; Olejniczak M; Huthoff H; Bielecki L; Pachulska-Wieczorek K; Das AT; Berkhout B; Adamiak RW (2003). "The apical loop of the HIV-1 TAR RNA hairpin is stabilized by a cross-loop base pair". J Biol Chem. 278 (40): 38892–38901. doi:10.1074/jbc.M301939200. PMID 12882959.
  3. Ouellet DL, Plante I, Landry P, et al. (April 2008). "Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element". Nucleic Acids Res. 36 (7): 2353–2365. doi:10.1093/nar/gkn076. PMC 2367715. PMID 18299284.
  4. Klase Z, Winograd R, Davis J, et al. (2009). "HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression". Retrovirology. 6: 18. doi:10.1186/1742-4690-6-18. PMC 2654423. PMID 19220914.
  5. Narayanan, A; Iordanskiy, S; Das, R; Van Duyne, R; Santos, S; Jaworski, E; Guendel, I; Sampey, G; Dalby, E; Iglesias-Ussel, M; Popratiloff, A; Hakami, R; Kehn-Hall, K; Young, M; Subra, C; Gilbert, C; Bailey, C; Romerio, F; Kashanchi, F (5 July 2013). "Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA". The Journal of Biological Chemistry. 288 (27): 20014–20033. doi:10.1074/jbc.m112.438895. PMC 3707700. PMID 23661700.
  6. Chowdhury, Mashiul; Taylor, J. Paul; Chang, Chun-Fan; Rappaport, Jay; Khalili, Kamel (1992). "Evidence that a Sequence Similar to TAR Is Important for Induction of the JC Virus Late Promoter by Human Immunodeficiency Virus Type 1 Tat". Journal of Virology. 66 (12): 7355–7361. doi:10.1128/jvi.66.12.7355-7361.1992. PMC 240440. PMID 1331525.
  7. Nukuzuma, Souichi; Kameoka, Masanori; Sugiura, Shigeki; Nakamichi, Kazuo; Nukuzuma, Chiyoko; Miyoshi, Isao; Takegami, Tsutomu (2012). "Exogenous human immunodeficiency virus-1 protein, Tat, enhances replication of JC virus efficiently in neuroblastoma cell lines". Journal of Medical Virology. 84 (4): 555–561. doi:10.1002/jmv.23239. PMID 22337293. S2CID 35625307.
  8. Krachmarov, Chavdar P.; Chepenik, Lara G.; Barr-Vagell, Sharon; Khalili, Kamel; Johnson, Edward M. (1996). "Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Purα". Proceedings of the National Academy of Sciences of the United States of America. 93 (24): 14112–14117. doi:10.1073/pnas.93.24.14112. PMC 34556. PMID 8943069.
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