A Zinc Finger Protein, TbZC3H20, Stabilizes Two Developmentally Regulated mRNAs in Trypanosomes

Ling, Alexandra; Trotter, James R.; Hendriks, Edward F.

doi:10.1074/jbc.m110.139261

Cited by 43 publications

(54 citation statements)

References 54 publications

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“…ZFP1 was one of the first trypanosome RBPs to be implicated in development [56], was shown to be transiently upregulated during the differentiation from bloodstream to procyclic forms and consistent with our data was expressed at higher levels in established procyclic cells. ALBA2 was previously identified to interact with regulatory elements in the 3’ UTR of GPEET procyclin mRNA [57] and ZC3H20 is required for growth of procyclic forms [58], which fits our transcriptome data. Another noteworthy RBP is PUF9 (Tb927.1.2600), which was most prominent in the proventriculus transcriptome.…”

Section: Resultssupporting

confidence: 82%

Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

et al. 2016

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African trypanosomes, the causative agents of sleeping sickness in humans and nagana in animals, have a complex digenetic life cycle between a mammalian host and an insect vector, the blood-feeding tsetse fly. Although the importance of the insect vector to transmit the disease was first realized over a century ago, many aspects of trypanosome development in tsetse have not progressed beyond a morphological analysis, mainly due to considerable challenges to obtain sufficient material for molecular studies. Here, we used high-throughput RNA-Sequencing (RNA-Seq) to profile Trypanosoma brucei transcript levels in three distinct tissues of the tsetse fly, namely the midgut, proventriculus and salivary glands. Consistent with current knowledge and providing a proof of principle, transcripts coding for procyclin isoforms and several components of the cytochrome oxidase complex were highly up-regulated in the midgut transcriptome, whereas transcripts encoding metacyclic VSGs (mVSGs) and the surface coat protein brucei alanine rich protein or BARP were extremely up-regulated in the salivary gland transcriptome. Gene ontology analysis also supported the up-regulation of biological processes such as DNA metabolism and DNA replication in the proventriculus transcriptome and major changes in signal transduction and cyclic nucleotide metabolism in the salivary gland transcriptome. Our data highlight a small repertoire of expressed mVSGs and potential signaling pathways involving receptor-type adenylate cyclases and members of a surface carboxylate transporter family, called PADs (Proteins Associated with Differentiation), to cope with the changing environment, as well as RNA-binding proteins as a possible global regulators of gene expression.

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Section: Resultssupporting

confidence: 82%

Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

et al. 2016

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“…ZC3H21 also was found to bind the EP2 mRNA; binding by ZC3H20 was just below our cut‐off. The two mRNAs that Ling et al () had previously shown to be bound to ZC3H20, encoding a trans ‐sialidase (Tb927.5.440) and the mitochondrial carrier MCP12 (Tb927.10.12840), were bound to both ZC3H21 and ZC3H20 in our analysis. We independently confirmed binding of ZC3H20 to the mRNAs encoding Aquaporin 1 and GPEET procyclin by pull‐down followed by semi‐quantitative PCR: Figure b shows that these two mRNAs were enriched relative to the tubulin control.…”

Section: Resultssupporting

confidence: 55%

“…Ling et al (Ling, Trotter, & Hendriks, ) showed that RNAi that simultaneously targeted ZC3H20 and ZC3H21 inhibited procyclic form trypanosome growth. Microarray experiments revealed that RNAi resulted in reduced levels of six RNAs, and increases in another ten.…”

Section: Introductionmentioning

confidence: 99%

The zinc finger proteins ZC3H20 and ZC3H21 stabilise mRNAs encoding membrane proteins and mitochondrial proteins in insect‐form Trypanosoma brucei

Liu

Marucha

Clayton

2019

Molecular Microbiology

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ZC3H20 and ZC3H21 are related trypanosome proteins with two C(x)8C(x)5C(x)3H zinc finger motifs. ZC3H20 is present at a low level in replicating mammalian‐infective bloodstream forms, but becomes more abundant when they undergo growth arrest at high density; ZC3H21 appears only in the procyclic form of the parasite, which infects Tsetse flies. Each protein binds to several hundred mRNAs, with overlapping but not identical specificities. Both increase expression of bound mRNAs, probably through recruitment of the MKT1‐PBP1 complex. At least 28 of the bound mRNAs decrease after depletion of ZC3H20, or of ZC3H20 and ZC3H21 together; their products include procyclic‐specific proteins of the plasma membrane and energy metabolism. Simultaneous depletion of ZC3H20 and ZC3H21 causes procyclic forms to shrink and stop growing; in addition to decreases in target mRNAs, there are other changes suggestive of loss of developmental regulation. The bloodstream‐form‐specific protein RBP10 controls ZC3H20 and ZC3H21 expression. Interestingly, some ZC3H20/21 target mRNAs also bind to and are repressed by RBP10, allowing for dynamic regulation as RBP10 decreases and ZC3H20 and ZC3H21 increase during differentiation.

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“…T. brucei has forty-nine CCCH zinc finger proteins, some of which have been implicated in control of gene expression [33], [34], [35], [36], [37], [38], [39]. So far, however, none has been shown to have a destabilising function.…”

Section: Introductionmentioning

confidence: 99%

Post-Transcriptional Regulation of the Trypanosome Heat Shock Response by a Zinc Finger Protein

et al. 2013

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In most organisms, the heat-shock response involves increased heat-shock gene transcription. In Kinetoplastid protists, however, virtually all control of gene expression is post-transcriptional. Correspondingly, Trypanosoma brucei heat-shock protein 70 (HSP70) synthesis after heat shock depends on regulation of HSP70 mRNA turnover. We here show that the T. brucei CCCH zinc finger protein ZC3H11 is a post-transcriptional regulator of trypanosome chaperone mRNAs. ZC3H11 is essential in bloodstream-form trypanosomes and for recovery of insect-form trypanosomes from heat shock. ZC3H11 binds to mRNAs encoding heat-shock protein homologues, with clear specificity for the subset of trypanosome chaperones that is required for protein refolding. In procyclic forms, ZC3H11 was required for stabilisation of target chaperone-encoding mRNAs after heat shock, and the HSP70 mRNA was also decreased upon ZC3H11 depletion in bloodstream forms. Many mRNAs bound to ZC3H11 have a consensus AUU repeat motif in the 3′-untranslated region. ZC3H11 bound preferentially to AUU repeats in vitro, and ZC3H11 regulation of HSP70 mRNA in bloodstream forms depended on its AUU repeat region. Tethering of ZC3H11 to a reporter mRNA increased reporter expression, showing that it is capable of actively stabilizing an mRNA. These results show that expression of trypanosome heat-shock genes is controlled by a specific RNA-protein interaction. They also show that heat-shock-induced chaperone expression in procyclic trypanosome enhances parasite survival at elevated temperatures.

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A Zinc Finger Protein, TbZC3H20, Stabilizes Two Developmentally Regulated mRNAs in Trypanosomes

Cited by 43 publications

References 54 publications

Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

The zinc finger proteins ZC3H20 and ZC3H21 stabilise mRNAs encoding membrane proteins and mitochondrial proteins in insect‐form Trypanosoma brucei

Post-Transcriptional Regulation of the Trypanosome Heat Shock Response by a Zinc Finger Protein

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