The RNA-binding protein RBP33 dampens non-productive transcription in trypanosomes

Gómez-Liñán, Claudia; Gómez-Díaz, Elena; Ceballos-Pérez, Gloria; Fernández‐Moya, Sandra M.; Estévez, Antonio M.

doi:10.1093/nar/gkac1123

Cited by 2 publications

(1 citation statement)

References 77 publications

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“…On another note, how trypanosomes regulate their gene could depend on ribosomal RNA-binding proteins (RBPs) since they act as modulators of mRNA abundance [63], leave alone promoting cell differentiation [64,65]. Disruption of RBP33 in trypanosomes results in overexpression of approximately 40% of all annotated genes in the genome [66]. Moreover, the knockout of three RBPs, TcZC3H39, TcZC3H29, and TcZC3HTTP, in T. cruzi using CRISPR-Cas9, resulted in morphological changes of the parasite, suggesting the significance of RBPs in parasite survival [67].…”

Section: Gene Regulationmentioning

confidence: 99%

Possible Chemotherapeutic Potential of Inhibiting N-Alpha Terminal Acetylation Activities to Combat Trypanosome Infections

Ochaya

2023

Infectious Diseases

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New anti-trypanosome drugs focusing on N-alpha terminal acetylation (Nt-acetylation) interference are necessary scientific inputs because currently, many of the drugs in use are unacceptably toxic; moreover, resistance is emerging. Nt-acetylation transfers an acetyl molecule to the N-alpha terminal of a protein by enzymes called N-alpha terminal acetyltransferases (Nats). Nats are grouped according to their amino acid sequence at the N-terminus where they acetylate. It is conserved in all kingdoms of life, and in humans, approximately 80% of proteins are thought to be Nt-acetylated. NatA-NatF and NatH identified in humans, and NatG has been observed in plants. Nats play critical roles in several cellular processes and integrity and have been suggested as possible drug targets to control different cancer diseases. NatA and NatC have been partially characterized in trypanosomes and shown to be essential for parasite viability. Biologically, the way parasites program their lives is embedded in their unique organelles, metabolic pathways, gene regulation, epigenetic gene activities, and many virulence factors including surface molecules. These characteristics and the different protein-coding genes involved could be Nt-acetylated, and the inhibition of Nats can deny the ability of trypanosomes to survive in any environment because many proteins can be simultaneously affected.

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Section: Gene Regulationmentioning

confidence: 99%

Possible Chemotherapeutic Potential of Inhibiting N-Alpha Terminal Acetylation Activities to Combat Trypanosome Infections

Ochaya

2023

Infectious Diseases

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Role of the RNA-binding protein ZC3H41 in the regulation of ribosomal protein messenger RNAs in trypanosomes

et al. 2023

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Background Trypanosomes are single-celled eukaryotes that rely heavily on post-transcriptional mechanisms to regulate gene expression. RNA-binding proteins play essential roles in regulating the fate, abundance and translation of messenger RNAs (mRNAs). Among these, zinc finger proteins of the cysteine3histidine (CCCH) class have been shown to be key players in cellular processes as diverse as differentiation, regulation of the cell cycle and translation. ZC3H41 is an essential zinc finger protein that has been described as a component of spliced leader RNA granules and nutritional stress granules, but its role in RNA metabolism is unknown. Methods Cell cycle analysis in ZC3H41- and Z41AP-depleted cells was carried out using 4′,6-diamidino-2-phenylindole staining, microscopic examination and flow cytometry. The identification of ZC3H41 protein partners was done using tandem affinity purification and mass spectrometry. Next-generation sequencing was used to evaluate the effect of ZC3H41 depletion on the transcriptome of procyclic Trypanosoma brucei cells, and also to identify the cohort of mRNAs associated with the ZC3H41/Z41AP complex. Levels of 5S ribosomal RNA (rRNA) species in ZC3H41- and Z41AP-depleted cells were assessed by quantitative reverse transcription-polymerase chain reaction. Surface sensing of translation assays were used to monitor global translation. Results We showed that depletion of the zinc finger protein ZC3H41 resulted in marked cell cycle defects and abnormal cell morphologies. ZC3H41 was found associated with an essential protein, which we named Z41AP, forming a stable heterodimer, and also with proteins of the poly(A)-binding protein 1 complex. The identification of mRNAs associated with the ZC3H41/Z41AP complex revealed that it is primarily composed of ribosomal protein mRNAs, and that binding to target transcripts is diminished upon nutritional stress. In addition, we observed that mRNAs encoding several proteins involved in the maturation of 5S rRNA are also associated with the ZC3H41/Z41AP complex. Finally, we showed that depletion of either ZC3H41 or Z41AP led to the accumulation of 5S rRNA precursors and a decrease of protein translation. Conclusions We propose that ZC3H41 and Z41AP play important roles in controlling the fate of ribosomal components in response to environmental cues. Graphical Abstract

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The RNA-binding protein RBP33 dampens non-productive transcription in trypanosomes

Cited by 2 publications

References 77 publications

Possible Chemotherapeutic Potential of Inhibiting N-Alpha Terminal Acetylation Activities to Combat Trypanosome Infections

Possible Chemotherapeutic Potential of Inhibiting N-Alpha Terminal Acetylation Activities to Combat Trypanosome Infections

Role of the RNA-binding protein ZC3H41 in the regulation of ribosomal protein messenger RNAs in trypanosomes

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