Interactions of the Zinc-finger-domain Protein ZC3H28

Overview

Journal Parasitology

Specialty Parasitology

Date 2022 Mar 10

PMID 35264260

Authors

Tania Bishola Tshitenge

Christine Clayton

Affiliations

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Abstract

In Trypanosoma brucei and related Kinetoplastids, regulation of gene expression occurs mostly post-transcriptionally, and RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Trypanosoma brucei ZC3H28 is a 114 KDa cytoplasmic mRNA-binding protein with a single C(x)7C(x)5C(x)sH zinc finger at the C-terminus and numerous proline-, histidine- or glutamine-rich regions. ZC3H28 is essential for normal bloodstream-form trypanosome growth, and when tethered to a reporter mRNA, ZC3H28 increased reporter mRNA and protein levels. Purification of N-terminally tagged ZC3H28 followed by mass spectrometry showed enrichment of ribosomal proteins, various RNA-binding proteins including both poly(A) binding proteins, the translation initiation complex EIF4E4/EIF4G3, and the activator MKT1. Tagged ZC3H28 was preferentially associated with long RNAs that have low complexity sequences in their 3′-untranslated regions; their coding regions also have low ribosome densities. In agreement with the tethering results, after ZC3H28 depletion, the levels of a significant proportion of its bound mRNAs decreased. We suggest that ZC3H28 is implicated in the stabilization of long mRNAs that are poorly translated.

Citing Articles

Genome-scale RNA interference profiling of Trypanosoma brucei cell cycle progression defects.

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The RNA-binding protein DRBD18 ensures correct mRNA splicing and polyadenylation patterns.

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References

Khong A, Parker R . The landscape of eukaryotic mRNPs. RNA. 2019; 26(3):229-239. PMC: 7025503. DOI: 10.1261/rna.073601.119. View

Gupta S, Kosti I, Plaut G, Pivko A, Tkacz I, Cohen-Chalamish S . The hnRNP F/H homologue of Trypanosoma brucei is differentially expressed in the two life cycle stages of the parasite and regulates splicing and mRNA stability. Nucleic Acids Res. 2013; 41(13):6577-94. PMC: 3711420. DOI: 10.1093/nar/gkt369. View

Ooi C, Benz C, Urbaniak M . Phosphoproteomic analysis of mammalian infective Trypanosoma brucei subjected to heat shock suggests atypical mechanisms for thermotolerance. J Proteomics. 2020; 219:103735. DOI: 10.1016/j.jprot.2020.103735. View

Vigneron A, ONeill M, Weiss B, Savage A, Campbell O, Kamhawi S . Single-cell RNA sequencing of from tsetse salivary glands unveils metacyclogenesis and identifies potential transmission blocking antigens. Proc Natl Acad Sci U S A. 2020; 117(5):2613-2621. PMC: 7007551. DOI: 10.1073/pnas.1914423117. View

Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu D . The genome of the African trypanosome Trypanosoma brucei. Science. 2005; 309(5733):416-22. DOI: 10.1126/science.1112642. View

Ling A, Trotter J, Hendriks E . A zinc finger protein, TbZC3H20, stabilizes two developmentally regulated mRNAs in trypanosomes. J Biol Chem. 2011; 286(23):20152-62. PMC: 3121479. DOI: 10.1074/jbc.M110.139261. View

Hudson B, Martinez-Yamout M, Dyson H, Wright P . Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. Nat Struct Mol Biol. 2004; 11(3):257-64. DOI: 10.1038/nsmb738. View

Dean S, Sunter J, Wheeler R . TrypTag.org: A Trypanosome Genome-wide Protein Localisation Resource. Trends Parasitol. 2016; 33(2):80-82. PMC: 5270239. DOI: 10.1016/j.pt.2016.10.009. View

Shi H, Ullu E, Tschudi C . Function of the Trypanosome Argonaute 1 protein in RNA interference requires the N-terminal RGG domain and arginine 735 in the Piwi domain. J Biol Chem. 2004; 279(48):49889-93. DOI: 10.1074/jbc.M409280200. View

10.

Lueong S, Merce C, Fischer B, Hoheisel J, Erben E . Gene expression regulatory networks in Trypanosoma brucei: insights into the role of the mRNA-binding proteome. Mol Microbiol. 2016; 100(3):457-71. DOI: 10.1111/mmi.13328. View

11.

Liu B, Kamanyi Marucha K, Clayton C . The zinc finger proteins ZC3H20 and ZC3H21 stabilise mRNAs encoding membrane proteins and mitochondrial proteins in insect-form Trypanosoma brucei. Mol Microbiol. 2019; 113(2):430-451. DOI: 10.1111/mmi.14429. View

12.

Alibu V, Storm L, Haile S, Clayton C, Horn D . A doubly inducible system for RNA interference and rapid RNAi plasmid construction in Trypanosoma brucei. Mol Biochem Parasitol. 2004; 139(1):75-82. DOI: 10.1016/j.molbiopara.2004.10.002. View

13.

Paterou A, Walrad P, Craddy P, Fenn K, Matthews K . Identification and stage-specific association with the translational apparatus of TbZFP3, a CCCH protein that promotes trypanosome life-cycle development. J Biol Chem. 2006; 281(51):39002-13. PMC: 2688685. DOI: 10.1074/jbc.M604280200. View

14.

Fadda A, Ryten M, Droll D, Rojas F, Farber V, Haanstra J . Transcriptome-wide analysis of trypanosome mRNA decay reveals complex degradation kinetics and suggests a role for co-transcriptional degradation in determining mRNA levels. Mol Microbiol. 2014; 94(2):307-26. PMC: 4285177. DOI: 10.1111/mmi.12764. View

15.

Erben E, Fadda A, Lueong S, Hoheisel J, Clayton C . A genome-wide tethering screen reveals novel potential post-transcriptional regulators in Trypanosoma brucei. PLoS Pathog. 2014; 10(6):e1004178. PMC: 4055773. DOI: 10.1371/journal.ppat.1004178. View

16.

Antwi E, Haanstra J, Ramasamy G, Jensen B, Droll D, Rojas F . Integrative analysis of the Trypanosoma brucei gene expression cascade predicts differential regulation of mRNA processing and unusual control of ribosomal protein expression. BMC Genomics. 2016; 17:306. PMC: 4845500. DOI: 10.1186/s12864-016-2624-3. View

17.

Naguleswaran A, Gunasekera K, Schimanski B, Heller M, Hemphill A, Ochsenreiter T . Trypanosoma brucei RRM1 is a nuclear RNA-binding protein and modulator of chromatin structure. mBio. 2015; 6(2):e00114. PMC: 4453557. DOI: 10.1128/mBio.00114-15. View

18.

Clayton C . Genetic manipulation of kinetoplastida. Parasitol Today. 1999; 15(9):372-8. DOI: 10.1016/s0169-4758(99)01498-2. View

19.

Freire E, Sturm N, Campbell D, de Melo Neto O . The Role of Cytoplasmic mRNA Cap-Binding Protein Complexes in Trypanosoma brucei and Other Trypanosomatids. Pathogens. 2017; 6(4). PMC: 5750579. DOI: 10.3390/pathogens6040055. View

20.

Alsford S, Turner D, Obado S, Sanchez-Flores A, Glover L, Berriman M . High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome. Genome Res. 2011; 21(6):915-24. PMC: 3106324. DOI: 10.1101/gr.115089.110. View