Molecular Functions and Potential Utilization of Zinc Finger Proteins in Protozoan Parasites
DOI:
https://doi.org/10.21467/exr.5.1.9879Abstract
Zinc finger proteins (ZFP) are metalloproteins whose zinc atom interacts with side chains of specific histidines and cysteines of the zinc finger motif, generating functional three dimensional structures. A good number of these proteins from different species are similar while others are divergent in structure and function. Existing literature on the structural features, functions of these proteins and their potential to be targeted for drug development or used as molecular tools in parasitic protozoa was explored. Evidence from reviewed articles revealed that, just like in other eukaryotes, these proteins function in various parasite cellular processes such as: transcription, RNA editing, mRNA processing & export and, mRNA turn-over among others. Some of them had the same structural features and function as their homologues in other eukaryotes including their hosts. However, there were others which had divergent structure and function. Some studies on drug development aiming at replacing the zinc atom reported positive results in some parasites such as Giardia lamblia, Trichomonas vaginalis and Leishmania donovani among others. However, though this is promising, the off- target challenge that can cause side effects, must be solved before wide application can be achieved. Successful engineering of these proteins and their use in genome editing was also reported in Plasmodium falciparum. Since zinc finger nucleases are a powerful research and medical tool, repurposing of the divergent ZFPs can be useful in the drug target and therapy discovery. For this to succeed, more knowledge on the specific functions of more parasite ZFPs and how their functions are regulated is needed.
Keywords:
ZFP, parasite, mRNADownloads
References
Abbehausen, C. (2019). Zinc finger domains as therapeutic targets for metal-based compounds—An update. Metallomics: Integrated Biometal Science, 11(1), 15–28. https://doi.org/10.1039/c8mt00262b
Addepalli, B., & Hunt, A. G. (2007). A novel endonuclease activity associated with the Arabidopsis ortholog of the 30-kDa subunit of cleavage and polyadenylation specificity factor. Nucleic Acids Research, 35(13), 4453–4463. https://doi.org/10.1093/nar/gkm457
Addepalli, B., & Hunt, A. G. (2008). Ribonuclease activity is a common property of Arabidopsis CCCH-containing zinc-finger proteins. FEBS Letters, 582(17), 2577–2582. https://doi.org/10.1016/j.febslet.2008.06.029
Aghaei, M., Aghaei, S., Kouhiyan, M., Shahmoradi, Z., & Hejazi, S. H. (2024). The Interaction of Zinc as an Essential Trace Element with Leishmania Parasites: A Systematic Review. Advanced Biomedical Research, 13, 73. https://doi.org/10.4103/abr.abr_187_23
Alves, L. R., Oliveira, C., Mörking, P. A., Kessler, R. L., Martins, S. T., Romagnoli, B. A. A., Marchini, F. K., & Goldenberg, S. (2014). The mRNAs associated to a zinc finger protein from Trypanosoma cruzi shift during stress conditions. RNA Biology, 11(7), 921–933. https://doi.org/10.4161/rna.29622
Babbarwal, V. K., Fleck, M., Ernst, N. L., Schnaufer, A., & Stuart, K. (2007). An essential role of KREPB4 in RNA editing and structural integrity of the editosome in Trypanosoma brucei. RNA (New York, N.Y.), 13(5), 737–744. https://doi.org/10.1261/rna.327707
Bai, C., & Tolias, P. P. (1996). Cleavage of RNA hairpins mediated by a developmentally regulated CCCH zinc finger protein. Molecular and Cellular Biology, 16(12), 6661–6667. https://doi.org/10.1128/MCB.16.12.6661
Barabino, S. M., Ohnacker, M., & Keller, W. (2000). Distinct roles of two Yth1p domains in 3’-end cleavage and polyadenylation of yeast pre-mRNAs. The EMBO Journal, 19(14), 3778–3787. https://doi.org/10.1093/emboj/19.14.3778
Benz, C., Engstler, M., Hillmer, S., & Clayton, C. (2010). Depletion of 14-3-3 proteins in bloodstream-form Trypanosoma brucei inhibits variant surface glycoprotein recycling. International Journal for Parasitology, 40(5), 629–634. https://doi.org/10.1016/j.ijpara.2009.10.015
Benz, C., Mulindwa, J., Ouna, B., & Clayton, C. (2011). The Trypanosoma brucei zinc finger protein ZC3H18 is involved in differentiation. Molecular and Biochemical Parasitology, 177(2), 148–151. https://doi.org/10.1016/j.molbiopara.2011.02.007
Bercovich, N., Levin, M. J., & Vazquez, M. P. (2009). The FIP-1 like polyadenylation factor in trypanosomes and the structural basis for its interaction with CPSF30. Biochemical and Biophysical Research Communications, 380(4), 850–855. https://doi.org/10.1016/j.bbrc.2009.01.182
Bhandari, D., Guha, K., Bhaduri, N., & Saha, P. (2011). Ubiquitination of mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) modulates the RNA endonuclease activity of its Smr domain. FEBS Letters, 585(5), 809–813. https://doi.org/10.1016/j.febslet.2011.02.007
Bhandari, D., & Saha, P. (2007). mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) is covalently modified by ubiquitination. FEMS Microbiology Letters, 273(2), 206–213. https://doi.org/10.1111/j.1574-6968.2007.00789.x
Brook, M., Tchen, C. R., Santalucia, T., McIlrath, J., Arthur, J. S. C., Saklatvala, J., & Clark, A. R. (2006). Posttranslational regulation of tristetraprolin subcellular localization and protein stability by p38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways. Molecular and Cellular Biology, 26(6), 2408–2418. https://doi.org/10.1128/MCB.26.6.2408-2418.2006
Brooks, S. A., & Blackshear, P. J. (2013). Tristetraprolin (TTP): Interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochimica Et Biophysica Acta, 1829(6–7), 666–679. https://doi.org/10.1016/j.bbagrm.2013.02.003
Brooks, S. A., Connolly, J. E., & Rigby, W. F. C. (2004). The role of mRNA turnover in the regulation of tristetraprolin expression: Evidence for an extracellular signal-regulated kinase-specific, AU-rich element-dependent, autoregulatory pathway. Journal of Immunology (Baltimore, Md.: 1950), 172(12), 7263–7271. https://doi.org/10.4049/jimmunol.172.12.7263
Brown, R. S. (2005). Zinc finger proteins: Getting a grip on RNA. Current Opinion in Structural Biology, 15(1), 94–98. https://doi.org/10.1016/j.sbi.2005.01.006
Calzavara-Silva, C. E., Prosdocimi, F., Abath, F. G. C., Pena, S. D. J., & Franco, G. R. (2004). Nucleic acid binding properties of SmZF1, a zinc finger protein of Schistosoma mansoni. International Journal for Parasitology, 34(11), 1211–1219. https://doi.org/10.1016/j.ijpara.2004.07.006
Carballo, E., Lai, W. S., & Blackshear, P. J. (2000). Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability. Blood, 95(6), 1891–1899.
Carnes, J., McDermott, S. M., Lewis, I., Tracy, M., & Stuart, K. (2022). Domain function and predicted structure of three heterodimeric endonuclease subunits of RNA editing catalytic complexes in Trypanosoma brucei. Nucleic Acids Research, 50(17), 10123–10139. https://doi.org/10.1093/nar/gkac753
Carnes, J., McDermott, S. M., & Stuart, K. (2023). RNA editing catalytic complexes edit multiple mRNA sites non-processively in Trypanosoma brucei. Molecular and Biochemical Parasitology, 256, 111596. https://doi.org/10.1016/j.molbiopara.2023.111596
Carnes, J., Schnaufer, A., McDermott, S. M., Domingo, G., Proff, R., Steinberg, A. G., Kurtz, I., & Stuart, K. (2012). Mutational analysis of Trypanosoma brucei editosome proteins KREPB4 and KREPB5 reveals domains critical for function. RNA (New York, N.Y.), 18(10), 1897–1909. https://doi.org/10.1261/rna.035048.112
Carnes, J., Trotter, J. R., Ernst, N. L., Steinberg, A., & Stuart, K. (2005). An essential RNase III insertion editing endonuclease in Trypanosoma brucei. Proceedings of the National Academy of Sciences of the United States of America, 102(46), 16614–16619. https://doi.org/10.1073/pnas.0506133102
Carnes, J., Trotter, J. R., Peltan, A., Fleck, M., & Stuart, K. (2008). RNA editing in Trypanosoma brucei requires three different editosomes. Molecular and Cellular Biology, 28(1), 122–130. https://doi.org/10.1128/MCB.01374-07
Cassandri, M., Smirnov, A., Novelli, F., Pitolli, C., Agostini, M., Malewicz, M., Melino, G., & Raschellà, G. (2017). Zinc-finger proteins in health and disease. Cell Death Discovery, 3, 17071. https://doi.org/10.1038/cddiscovery.2017.71
Clayton, C. E. (2002). Life without transcriptional control? From fly to man and back again. The EMBO Journal, 21(8), 1881–1888. https://doi.org/10.1093/emboj/21.8.1881
Das, A., Li, H., Liu, T., & Bellofatto, V. (2006). Biochemical characterization of Trypanosoma brucei RNA polymerase II. Molecular and Biochemical Parasitology, 150(2), 201–210. https://doi.org/10.1016/j.molbiopara.2006.08.002
Delaney, K. J., Xu, R., Zhang, J., Li, Q. Q., Yun, K.-Y., Falcone, D. L., & Hunt, A. G. (2006). Calmodulin interacts with and regulates the RNA-binding activity of an Arabidopsis polyadenylation factor subunit. Plant Physiology, 140(4), 1507–1521. https://doi.org/10.1104/pp.105.070672
Dostalova, A., Käser, S., Cristodero, M., & Schimanski, B. (2013). The nuclear mRNA export receptor Mex67-Mtr2 of Trypanosoma brucei contains a unique and essential zinc finger motif. Molecular Microbiology, 88(4), 728–739. https://doi.org/10.1111/mmi.12217
Dragone, M., Grazioso, R., D’Abrosca, G., Baglivo, I., Iacovino, R., Esposito, S., Paladino, A., Pedone, P. V., Russo, L., Fattorusso, R., Malgieri, G., & Isernia, C. (2022). Copper (I) or (II) Replacement of the Structural Zinc Ion in the Prokaryotic Zinc Finger Ros Does Not Result in a Functional Domain. International Journal of Molecular Sciences, 23(19), 11010. https://doi.org/10.3390/ijms231911010
Droll, D., Minia, I., Fadda, A., Singh, A., Stewart, M., Queiroz, R., & Clayton, C. (2013). Post-transcriptional regulation of the trypanosome heat shock response by a zinc finger protein. PLoS Pathogens, 9(4), e1003286. https://doi.org/10.1371/journal.ppat.1003286
Drozdz, M., Palazzo, S. S., Salavati, R., O’Rear, J., Clayton, C., & Stuart, K. (2002). TbMP81 is required for RNA editing in Trypanosoma brucei. The EMBO Journal, 21(7), 1791–1799. https://doi.org/10.1093/emboj/21.7.1791
Drummond, M. G., Calzavara-Silva, C. E., D’Astolfo, D. S., Cardoso, F. C., Rajão, M. A., Mourão, M. M., Gava, E., Oliveira, S. C., Macedo, A. M., Machado, C. R., Pena, S. D. J., Kitten, G. T., & Franco, G. R. (2009). Molecular characterization of the Schistosoma mansoni zinc finger protein SmZF1 as a transcription factor. PLoS Neglected Tropical Diseases, 3(11), e547. https://doi.org/10.1371/journal.pntd.0000547
Eleutério de Souza, P. R., Valadão, A. F., Calzavara-Silva, C. E., Franco, G. R., de Morais, M. A., & Abath, F. G. (2001). Cloning and characterization of SmZF1, a gene encoding a Schistosoma mansoni zinc finger protein. Memorias Do Instituto Oswaldo Cruz, 96 Suppl, 123–130. https://doi.org/10.1590/s0074-02762001000900018
Farina, B., Fattorusso, R., & Pellecchia, M. (2011). Targeting zinc finger domains with small molecules: Solution structure and binding studies of the RanBP2-type zinc finger of RBM5. Chembiochem: A European Journal of Chemical Biology, 12(18), 2837–2845. https://doi.org/10.1002/cbic.201100582
Frézard, F., Silva, H., Pimenta, A. M. de C., Farrell, N., & Demicheli, C. (2012). Greater binding affinity of trivalent antimony to a CCCH zinc finger domain compared to a CCHC domain of kinetoplastid proteins. Metallomics: Integrated Biometal Science, 4(5), 433–440. https://doi.org/10.1039/c2mt00176d
Gil-Moles, M., Basu, U., Büssing, R., Hoffmeister, H., Türck, S., Varchmin, A., & Ott, I. (2020). Gold Metallodrugs to Target Coronavirus Proteins: Inhibitory Effects on the Spike-ACE2 Interaction and on PLpro Protease Activity by Auranofin and Gold Organometallics*. Chemistry (Weinheim an Der Bergstrasse, Germany), 26(66), 15140–15144. https://doi.org/10.1002/chem.202004112
Gissot, M., Hovasse, A., Chaloin, L., Schaeffer-Reiss, C., Van Dorsselaer, A., & Tomavo, S. (2017). An evolutionary conserved zinc finger protein is involved in Toxoplasma gondii mRNA nuclear export. Cellular Microbiology, 19(2). https://doi.org/10.1111/cmi.12644
Goodhew, E. B., & Secor, W. E. (2013). Drug library screening against metronidazole-sensitive and metronidazole-resistant Trichomonas vaginalis isolates. Sexually Transmitted Infections, 89(6), 479–484. https://doi.org/10.1136/sextrans-2013-051032
Gosztyla, M. L., Zhan, L., Olson, S., Wei, X., Naritomi, J., Nguyen, G., Street, L., Goda, G. A., Cavazos, F. F., Schmok, J. C., Jain, M., Uddin Syed, E., Kwon, E., Jin, W., Kofman, E., Tankka, A. T., Li, A., Gonzalez, V., Lécuyer, E., … Yeo, G. W. (2024). Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation. Molecular Cell, 84(19), 3826-3842.e8. https://doi.org/10.1016/j.molcel.2024.08.010
Guo, X., Ernst, N. L., & Stuart, K. D. (2008). The KREPA3 zinc finger motifs and OB-fold domain are essential for RNA editing and survival of Trypanosoma brucei. Molecular and Cellular Biology, 28(22), 6939–6953. https://doi.org/10.1128/MCB.01115-08
Gupta, S. K., Carmi, S., Waldman Ben-Asher, H., Tkacz, I. D., Naboishchikov, I., & Michaeli, S. (2013). Basal splicing factors regulate the stability of mature mRNAs in trypanosomes. The Journal of Biological Chemistry, 288(7), 4991–5006. https://doi.org/10.1074/jbc.M112.416578
Hajikhezri, Z., Darweesh, M., Akusjärvi, G., & Punga, T. (2020). Role of CCCH-Type Zinc Finger Proteins in Human Adenovirus Infections. Viruses, 12(11), 1322. https://doi.org/10.3390/v12111322
Hendriks, E. F., & Matthews, K. R. (2005). Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein. Molecular Microbiology, 57(3), 706–716. https://doi.org/10.1111/j.1365-2958.2005.04679.x
Hendriks, E. F., Robinson, D. R., Hinkins, M., & Matthews, K. R. (2001). A novel CCCH protein which modulates differentiation of Trypanosoma brucei to its procyclic form. The EMBO Journal, 20(23), 6700–6711. https://doi.org/10.1093/emboj/20.23.6700
Hudson, B. P., Martinez-Yamout, M. A., Dyson, H. J., & Wright, P. E. (2004). Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. Nature Structural & Molecular Biology, 11(3), 257–264. https://doi.org/10.1038/nsmb738
Ichikawa, D. M., Abdin, O., Alerasool, N., Kogenaru, M., Mueller, A. L., Wen, H., Giganti, D. O., Goldberg, G. W., Adams, S., Spencer, J. M., Razavi, R., Nim, S., Zheng, H., Gionco, C., Clark, F. T., Strokach, A., Hughes, T. R., Lionnet, T., Taipale, M., … Noyes, M. B. (2023). A universal deep-learning model for zinc finger design enables transcription factor reprogramming. Nature Biotechnology, 41(8), 1117–1129. https://doi.org/10.1038/s41587-022-01624-4
Inoue, M., Yasuda, K., Uemura, H., Yasaka, N., Inoue, H., Sei, Y., Horikoshi, N., & Fukuma, T. (2010). Phosphorylation-dependent protein interaction with Trypanosoma brucei 14-3-3 proteins that display atypical target recognition. PloS One, 5(12), e15566. https://doi.org/10.1371/journal.pone.0015566
Jen, J., & Wang, Y.-C. (2016). Zinc finger proteins in cancer progression. Journal of Biomedical Science, 23(1), 53. https://doi.org/10.1186/s12929-016-0269-9
Kajumbula, H., Byarugaba, W., & Wayengera, M. (2012). Targeting wild-type Erythrocyte receptors for Plasmodium falciparum and vivax Merozoites by Zinc Finger Nucleases In- silico: Towards a Genetic Vaccine against Malaria. Genetic Vaccines and Therapy, 10(1), 8. https://doi.org/10.1186/1479-0556-10-8
Kamaliyan, Z., & Clarke, T. L. (2024). Zinc finger proteins: Guardians of genome stability. Frontiers in Cell and Developmental Biology, 12, 1448789. https://doi.org/10.3389/fcell.2024.1448789
Kang, X., Falick, A. M., Nelson, R. E., Gao, G., Rogers, K., Aphasizhev, R., & Simpson, L. (2004). Disruption of the zinc finger motifs in the Leishmania tarentolae LC-4 (=TbMP63) L-complex editing protein affects the stability of the L-complex. The Journal of Biological Chemistry, 279(6), 3893–3899. https://doi.org/10.1074/jbc.M310185200
Kramer, S., Kimblin, N. C., & Carrington, M. (2010). Genome-wide in silico screen for CCCH-type zinc finger proteins of Trypanosoma brucei, Trypanosoma cruzi and Leishmania major. BMC Genomics, 11, 283. https://doi.org/10.1186/1471-2164-11-283
Krishna, S. S., Majumdar, I., & Grishin, N. V. (2003). Structural classification of zinc fingers: Survey and summary. Nucleic Acids Research, 31(2), 532–550. https://doi.org/10.1093/nar/gkg161
Lai, W. S., Carballo, E., Strum, J. R., Kennington, E. A., Phillips, R. S., & Blackshear, P. J. (1999). Evidence that tristetraprolin binds to AU-rich elements and promotes the deadenylation and destabilization of tumor necrosis factor alpha mRNA. Molecular and Cellular Biology, 19(6), 4311–4323. https://doi.org/10.1128/MCB.19.6.4311
Lai, W. S., Carballo, E., Thorn, J. M., Kennington, E. A., & Blackshear, P. J. (2000). Interactions of CCCH zinc finger proteins with mRNA. Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA. The Journal of Biological Chemistry, 275(23), 17827–17837. https://doi.org/10.1074/jbc.M001696200
Lai, W. S., Parker, J. S., Grissom, S. F., Stumpo, D. J., & Blackshear, P. J. (2006). Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of stabilized transcripts in TTP-deficient fibroblasts. Molecular and Cellular Biology, 26(24), 9196–9208. https://doi.org/10.1128/MCB.00945-06
Lane, J. E., Ribeiro-Rodrigues, R., Suarez, C. C., Bogitsh, B. J., Jones, M. M., Singh, P. K., & Carter, C. E. (1996). In vitro trypanocidal activity of tetraethylthiuram disulfide and sodium diethylamine-N-carbodithioate on Trypanosoma cruzi. The American Journal of Tropical Medicine and Hygiene, 55(3), 263–266. https://doi.org/10.4269/ajtmh.1996.55.263
Lerch, M., Carnes, J., Acestor, N., Guo, X., Schnaufer, A., & Stuart, K. (2012). Editosome accessory factors KREPB9 and KREPB10 in Trypanosoma brucei. Eukaryotic Cell, 11(7), 832–843. https://doi.org/10.1128/EC.00046-12
Li, C.-H., Irmer, H., Gudjonsdottir-Planck, D., Freese, S., Salm, H., Haile, S., Estévez, A. M., & Clayton, C. (2006). Roles of a Trypanosoma brucei 5’->3’ exoribonuclease homolog in mRNA degradation. RNA (New York, N.Y.), 12(12), 2171–2186. https://doi.org/10.1261/rna.291506
Li, L., Krymskaya, L., Wang, J., Henley, J., Rao, A., Cao, L.-F., Tran, C.-A., Torres-Coronado, M., Gardner, A., Gonzalez, N., Kim, K., Liu, P.-Q., Hofer, U., Lopez, E., Gregory, P. D., Liu, Q., Holmes, M. C., Cannon, P. M., Zaia, J. A., & DiGiusto, D. L. (2013). Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases. Molecular Therapy: The Journal of the American Society of Gene Therapy, 21(6), 1259–1269. https://doi.org/10.1038/mt.2013.65
Li, X., Han, M., Zhang, H., Liu, F., Pan, Y., Zhu, J., Liao, Z., Chen, X., & Zhang, B. (2022). Structures and biological functions of zinc finger proteins and their roles in hepatocellular carcinoma. Biomarker Research, 10(1), 2. https://doi.org/10.1186/s40364-021-00345-1
Ling, A. S., Trotter, J. R., & Hendriks, E. F. (2011). A zinc finger protein, TbZC3H20, stabilizes two developmentally regulated mRNAs in trypanosomes. The Journal of Biological Chemistry, 286(23), 20152–20162. https://doi.org/10.1074/jbc.M110.139261
Liu, B., Kamanyi Marucha, K., & Clayton, C. (2020). The zinc finger proteins ZC3H20 and ZC3H21 stabilise mRNAs encoding membrane proteins and mitochondrial proteins in insect-form Trypanosoma brucei. Molecular Microbiology, 113(2), 430–451. https://doi.org/10.1111/mmi.14429
Liu, S., Liu, X., Lin, X., & Chen, H. (2023). Zinc Finger Proteins in the War on Gastric Cancer: Molecular Mechanism and Clinical Potential. Cells, 12(9), 1314. https://doi.org/10.3390/cells12091314
Lykke-Andersen, J., & Wagner, E. (2005). Recruitment and activation of mRNA decay enzymes by two ARE-mediated decay activation domains in the proteins TTP and BRF-1. Genes & Development, 19(3), 351–361. https://doi.org/10.1101/gad.1282305
Manful, T., Fadda, A., & Clayton, C. (2011). The role of the 5’-3’ exoribonuclease XRNA in transcriptome-wide mRNA degradation. RNA (New York, N.Y.), 17(11), 2039–2047. https://doi.org/10.1261/rna.2837311
McDonnell, N. B., De Guzman, R. N., Rice, W. G., Turpin, J. A., & Summers, M. F. (1997). Zinc ejection as a new rationale for the use of cystamine and related disulfide-containing antiviral agents in the treatment of AIDS. Journal of Medicinal Chemistry, 40(13), 1969–1976. https://doi.org/10.1021/jm970147+
McMahon, M. A., Rahdar, M., & Porteus, M. (2011). Gene editing: Not just for translation anymore. Nature Methods, 9(1), 28–31. https://doi.org/10.1038/nmeth.1811
Midlej, V., Rubim, F., Villarreal, W., Martins-Duarte, É. S., Navarro, M., de Souza, W., & Benchimol, M. (2019). Zinc-clotrimazole complexes are effective against Trichomonas vaginalis. Parasitology, 146(9), 1206–1216. https://doi.org/10.1017/S003118201900043X
Momin, T., Villasenor, A., Singh, A., Darweesh, M., Singh, A., & Rajput, M. (2023). ZFP36 ring finger protein like 1 significantly suppresses human coronavirus OC43 replication. PeerJ, 11, e14776. https://doi.org/10.7717/peerj.14776
Moraes Barros, R. R., Straimer, J., Sa, J. M., Salzman, R. E., Melendez-Muniz, V. A., Mu, J., Fidock, D. A., & Wellems, T. E. (2015). Editing the Plasmodium vivax genome, using zinc-finger nucleases. The Journal of Infectious Diseases, 211(1), 125–129. https://doi.org/10.1093/infdis/jiu423
Mörking, P. A., Rampazzo, R. de C. P., Walrad, P., Probst, C. M., Soares, M. J., Gradia, D. F., Pavoni, D. P., Krieger, M. A., Matthews, K., Goldenberg, S., Fragoso, S. P., & Dallagiovanna, B. (2012). The zinc finger protein TcZFP2 binds target mRNAs enriched during Trypanosoma cruzi metacyclogenesis. Memorias Do Instituto Oswaldo Cruz, 107(6), 790–799. https://doi.org/10.1590/s0074-02762012000600014
Nain, V., Sahi, S., & Verma, A. (2010). CPP-ZFN: A potential DNA-targeting anti-malarial drug. Malaria Journal, 9, 258. https://doi.org/10.1186/1475-2875-9-258
Nakata, E., Liew, F. F., Uwatoko, C., Kiyonaka, S., Mori, Y., Katsuda, Y., Endo, M., Sugiyama, H., & Morii, T. (2012). Zinc-finger proteins for site-specific protein positioning on DNA-origami structures. Angewandte Chemie (International Ed. in English), 51(10), 2421–2424. https://doi.org/10.1002/anie.201108199
Nash, T., & Rice, W. G. (1998). Efficacies of zinc-finger-active drugs against Giardia lamblia. Antimicrobial Agents and Chemotherapy, 42(6), 1488–1492. https://doi.org/10.1128/AAC.42.6.1488
Negi, S., Imanishi, M., Hamori, M., Kawahara-Nakagawa, Y., Nomura, W., Kishi, K., Shibata, N., & Sugiura, Y. (2023). The past, present, and future of artificial zinc finger proteins: Design strategies and chemical and biological applications. JBIC Journal of Biological Inorganic Chemistry, 28(3), 249–261. https://doi.org/10.1007/s00775-023-01991-6
Nett, I. R. E., Martin, D. M. A., Miranda-Saavedra, D., Lamont, D., Barber, J. D., Mehlert, A., & Ferguson, M. A. J. (2009). The phosphoproteome of bloodstream form Trypanosoma brucei, causative agent of African sleeping sickness. Molecular & Cellular Proteomics: MCP, 8(7), 1527–1538. https://doi.org/10.1074/mcp.M800556-MCP200
Ngwa, C. J., Farrukh, A., & Pradel, G. (2021). Zinc finger proteins of Plasmodium falciparum. Cellular Microbiology, 23(12), e13387. https://doi.org/10.1111/cmi.13387
Nomura, W., & Sugiura, Y. (2007). Design and synthesis of artificial zinc finger proteins. Methods in Molecular Biology (Clifton, N.J.), 352, 83–93. https://doi.org/10.1385/1-59745-187-8:83
Ok, K., Filipovic, M. R., & Michel, S. L. J. (2021). Targeting Zinc Finger Proteins with Exogenous Metals and Molecules: Lessons learned from Tristetraprolin, a CCCH type Zinc Finger. European Journal of Inorganic Chemistry, 2021(37), 3795–3805. https://doi.org/10.1002/ejic.202100402
Ouna, B. A., Stewart, M., Helbig, C., & Clayton, C. (2012). The Trypanosoma brucei CCCH zinc finger proteins ZC3H12 and ZC3H13. Molecular and Biochemical Parasitology, 183(2), 184–188. https://doi.org/10.1016/j.molbiopara.2012.02.006
Panigrahi, A. K., Schnaufer, A., Carmean, N., Igo, R. P., Gygi, S. P., Ernst, N. L., Palazzo, S. S., Weston, D. S., Aebersold, R., Salavati, R., & Stuart, K. D. (2001). Four related proteins of the Trypanosoma brucei RNA editing complex. Molecular and Cellular Biology, 21(20), 6833–6840. https://doi.org/10.1128/MCB.21.20.6833-6840.2001
Papworth, M., Kolasinska, P., & Minczuk, M. (2006). Designer zinc-finger proteins and their applications. Gene, 366(1), 27–38. https://doi.org/10.1016/j.gene.2005.09.011
Paterou, A., Walrad, P., Craddy, P., Fenn, K., & Matthews, K. (2006). Identification and stage-specific association with the translational apparatus of TbZFP3, a CCCH protein that promotes trypanosome life-cycle development. The Journal of Biological Chemistry, 281(51), 39002–39013. https://doi.org/10.1074/jbc.M604280200
Perdigão, P. R. L., Cunha-Santos, C., Barbas, C. F., Santa-Marta, M., & Goncalves, J. (2020). Protein Delivery of Cell-Penetrating Zinc-Finger Activators Stimulates Latent HIV-1-Infected Cells. Molecular Therapy. Methods & Clinical Development, 18, 145–158. https://doi.org/10.1016/j.omtm.2020.05.016
Perez, E. E., Wang, J., Miller, J. C., Jouvenot, Y., Kim, K. A., Liu, O., Wang, N., Lee, G., Bartsevich, V. V., Lee, Y.-L., Guschin, D. Y., Rupniewski, I., Waite, A. J., Carpenito, C., Carroll, R. G., Orange, J. S., Urnov, F. D., Rebar, E. J., Ando, D., … June, C. H. (2008). Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nature Biotechnology, 26(7), 808–816. https://doi.org/10.1038/nbt1410
Qu, X., Wang, P., Ding, D., Li, L., Wang, H., Ma, L., Zhou, X., Liu, S., Lin, S., Wang, X., Zhang, G., Liu, S., Liu, L., Wang, J., Zhang, F., Lu, D., & Zhu, H. (2013). Zinc-finger-nucleases mediate specific and efficient excision of HIV-1 proviral DNA from infected and latently infected human T cells. Nucleic Acids Research, 41(16), 7771–7782. https://doi.org/10.1093/nar/gkt571
Saini, S., Bharati, K., Shaha, C., & Mukhopadhyay, C. K. (2017). Zinc depletion promotes apoptosis-like death in drug-sensitive and antimony-resistance Leishmania donovani. Scientific Reports, 7(1), 10488. https://doi.org/10.1038/s41598-017-10041-6
Scheibel, L. W., Adler, A., & Trager, W. (1979). Tetraethylthiuram disulfide (Antabuse) inhibits the human malaria parasite Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America, 76(10), 5303–5307. https://doi.org/10.1073/pnas.76.10.5303
Schiffer, J. T., Aubert, M., Weber, N. D., Mintzer, E., Stone, D., & Jerome, K. R. (2012). Targeted DNA mutagenesis for the cure of chronic viral infections. Journal of Virology, 86(17), 8920–8936. https://doi.org/10.1128/JVI.00052-12
Schimanski, B., Brandenburg, J., Nguyen, T. N., Caimano, M. J., & Günzl, A. (2006). A TFIIB-like protein is indispensable for spliced leader RNA gene transcription in Trypanosoma brucei. Nucleic Acids Research, 34(6), 1676–1684. https://doi.org/10.1093/nar/gkl090
Schmidlin, M., Lu, M., Leuenberger, S. A., Stoecklin, G., Mallaun, M., Gross, B., Gherzi, R., Hess, D., Hemmings, B. A., & Moroni, C. (2004). The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B. The EMBO Journal, 23(24), 4760–4769. https://doi.org/10.1038/sj.emboj.7600477
Schnaufer, A., Wu, M., Park, Y., Nakai, T., Deng, J., Proff, R., Hol, W. G. J., & Stuart, K. D. (2010). A protein-protein interaction map of trypanosome ~20S editosomes. The Journal of Biological Chemistry, 285(8), 5282–5295. https://doi.org/10.1074/jbc.M109.059378
Schwede, A., Manful, T., Jha, B. A., Helbig, C., Bercovich, N., Stewart, M., & Clayton, C. (2009). The role of deadenylation in the degradation of unstable mRNAs in trypanosomes. Nucleic Acids Research, 37(16), 5511–5528. https://doi.org/10.1093/nar/gkp571
Stoecklin, G., Colombi, M., Raineri, I., Leuenberger, S., Mallaun, M., Schmidlin, M., Gross, B., Lu, M., Kitamura, T., & Moroni, C. (2002). Functional cloning of BRF1, a regulator of ARE-dependent mRNA turnover. The EMBO Journal, 21(17), 4709–4718. https://doi.org/10.1093/emboj/cdf444
Straimer, J., Lee, M. C. S., Lee, A. H., Zeitler, B., Williams, A. E., Pearl, J. R., Zhang, L., Rebar, E. J., Gregory, P. D., Llinás, M., Urnov, F. D., & Fidock, D. A. (2012). Site-specific genome editing in Plasmodium falciparum using engineered zinc-finger nucleases. Nature Methods, 9(10), 993–998. https://doi.org/10.1038/nmeth.2143
Sun, L., Stoecklin, G., Van Way, S., Hinkovska-Galcheva, V., Guo, R.-F., Anderson, P., & Shanley, T. P. (2007). Tristetraprolin (TTP)-14-3-3 complex formation protects TTP from dephosphorylation by protein phosphatase 2a and stabilizes tumor necrosis factor-alpha mRNA. The Journal of Biological Chemistry, 282(6), 3766–3777. https://doi.org/10.1074/jbc.M607347200
Tchen, C. R., Brook, M., Saklatvala, J., & Clark, A. R. (2004). The stability of tristetraprolin mRNA is regulated by mitogen-activated protein kinase p38 and by tristetraprolin itself. The Journal of Biological Chemistry, 279(31), 32393–32400. https://doi.org/10.1074/jbc.M402059200
Torres-Romero, J. C., Villalpando, J. L., Lara-Riegos, J., Valdés, J., Azuara-Liceaga, E., Euan-Canto, A., López-Camarillo, C., & Alvarez-Sánchez, M. E. (2020). In silico analysis of putative metal response elements (MREs) in the zinc-responsive genes from Trichomonas vaginalis and the identification of novel palindromic MRE-like motif. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 33(4–5), 229–240. https://doi.org/10.1007/s10534-020-00246-0
Trotter, J. R., Ernst, N. L., Carnes, J., Panicucci, B., & Stuart, K. (2005). A deletion site editing endonuclease in Trypanosoma brucei. Molecular Cell, 20(3), 403–412. https://doi.org/10.1016/j.molcel.2005.09.016
Vazquez, M. P., Mualem, D., Bercovich, N., Stern, M. Z., Nyambega, B., Barda, O., Nasiga, D., Gupta, S. K., Michaeli, S., & Levin, M. J. (2009). Functional characterization and protein-protein interactions of trypanosome splicing factors U2AF35, U2AF65 and SF1. Molecular and Biochemical Parasitology, 164(2), 137–146. https://doi.org/10.1016/j.molbiopara.2008.12.009
Villalpando, J. L., Arreola, R., Puente-Rivera, J., Azuara-Liceaga, E., Valdés, J., López-Canovas, L., Villalobos-Osnaya, A., & Alvarez-Sánchez, M. E. (2017). TvZNF1 is a C2H2 zinc finger protein of Trichomonas vaginalis. Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine, 30(6), 861–872. https://doi.org/10.1007/s10534-017-0053-7
Walrad, P. B., Capewell, P., Fenn, K., & Matthews, K. R. (2012). The post-transcriptional trans-acting regulator, TbZFP3, co-ordinates transmission-stage enriched mRNAs in Trypanosoma brucei. Nucleic Acids Research, 40(7), 2869–2883. https://doi.org/10.1093/nar/gkr1106
Walrad, P., Paterou, A., Acosta-Serrano, A., & Matthews, K. R. (2009). Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements. PLoS Pathogens, 5(2), e1000317. https://doi.org/10.1371/journal.ppat.1000317
Worthey, E. A., Schnaufer, A., Mian, I. S., Stuart, K., & Salavati, R. (2003). Comparative analysis of editosome proteins in trypanosomatids. Nucleic Acids Research, 31(22), 6392–6408. https://doi.org/10.1093/nar/gkg870
Zhao, J., Wen, D., Zhang, S., Jiang, H., & Di, X. (2023). The role of zinc finger proteins in malignant tumors. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 37(9), e23157. https://doi.org/10.1096/fj.202300801R
Downloads
Published
Issue
Section
How to Cite
License
Copyright (c) 2025 Benard Aswani Ouna
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The author(s) retains full copyright of their article and grants non-exclusive publishing right to Extensive Reviews and its publisher AIJR (India). Author(s) can archive pre-print, post-print, and published version/PDF to any open access, institutional repository, social media, or personal website provided that Published source must be acknowledged with citation and link to publisher version.
Click here for more information on Copyright policy
Click here for more information on Licensing policy
