Gene duplication in trypanosomatids – Two DED1 paralogs are functionally redundant and differentially expressed during the life cycle

Zinoviev, Alexandra; Akum, Yael; Yahav, Tal; Shapira, Michael Y.

doi:10.1016/j.molbiopara.2012.08.001

Cited by 15 publications

(15 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Table 1, this includes 10 putative RNA helicases, a class of proteins that functions at every step of RNA metabolism in higher eukaryotes [35]. Two of these, TbDED1-1 and TbDED1-2, were recently shown to have partially redundant functions in translation [36], while MTR4 reportedly functions in rRNA processing [37]. Also identified as containing methylarginine were 10 RRM containing proteins.…”

Section: Resultsmentioning

confidence: 99%

Global proteomic analysis in trypanosomes reveals unique proteins and conserved cellular processes impacted by arginine methylation

Lott

Fisk

et al. 2013

Journal of Proteomics

View full text Add to dashboard Cite

Arginine methylation is a common posttranslational modification with reported functions in transcription, RNA processing and translation, and DNA repair. Trypanosomes encode five protein arginine methyltransferases, suggesting that arginine methylation exerts widespread impacts on the biology of these organisms. Here, we performed a global proteomic analysis of T. brucei to identify arginine methylated proteins and their sites of modification. Using an approach entailing two-dimensional chromatographic separation, and alternating electron transfer dissociation and collision induced dissociation, we identified 1332 methylarginines in 676 proteins. The resulting data set represents the largest compilation of arginine methylated proteins in any organism to date. Functional classification revealed numerous arginine methylated proteins involved in flagellar function, RNA metabolism, DNA replication and repair, and intracellular protein trafficking. Thus, arginine methylation has the potential to impact aspects of T. brucei gene expression, cell biology, and pathogenesis. Interestingly, pathways with known methylated proteins in higher eukaryotes were identified in this study, but often different components of the pathway were methylated in trypanosomes. Methylarginines were often identified in glycine rich contexts, although exceptions to this rule were detected. Collectively, these data inform on a multitude of aspects of trypanosome biology and serve as a guide for the identification of homologous arginine methylated proteins in higher eukaryotes.

show abstract

Section: Resultsmentioning

confidence: 99%

Global proteomic analysis in trypanosomes reveals unique proteins and conserved cellular processes impacted by arginine methylation

Lott

Fisk

et al. 2013

Journal of Proteomics

View full text Add to dashboard Cite

show abstract

“…These included three ATP-dependent DEAD/H RNA helicases (Tb927.3.2600, Tb927.8.1510 and Tb09.211.3510), two of which are potential homologues of yeast Ded1p and Dbp2p (34). We have, however, found the putative Ded1p homologue (Tb09.211.3510) in several other purifications, so the specificity of the interaction is unclear.…”

Section: Resultsmentioning

confidence: 99%

Trypanosome CNOT10 is essential for the integrity of the NOT deadenylase complex and for degradation of many mRNAs

Färber

Erben

Sharma

et al. 2012

Nucleic Acids Research

View full text Add to dashboard Cite

The degradation of most eukaryotic mRNAs is initiated by removal of the poly(A) tail, and the major deadenylase activity is associated with the CCR4/CAF1/NOT complex (NOT complex). We here study the role of CNOT10, a protein that is found in human and trypanosome, but not in yeast, NOT complexes. Trypanosome (Tb) CNOT10 is essential for growth. TbCNOT10 interacted with the deadenylase TbCAF1 and the scaffold protein TbNOT1; TbCAF1 also interacted with TbNOT1 in a yeast two-hybrid assay. In both trypanosomes and human embryonic kidney cells, approximately half of CAF1 was associated with the NOT complex. Depletion of CNOT10 from human cells did not affect this association. In contrast, depletion of TbCNOT10 in trypanosomes caused a decrease in the level of TbNOT1, detachment of TbCAF1 from the complex and pronounced stabilization of most trypanosome mRNAs. Artificial tethering of TbCAF1 to a reporter mRNA in vivo resulted in mRNA degradation, and this was not affected by TbCNOT10 depletion. We conclude that in trypanosomes, TbCNOT10 may stabilize the interaction between TbCAF1 and the NOT complex. The results further suggest that TbCAF1 is only able to deadenylate mRNA in vivo if it is recruited to the mRNA through other NOT complex components.

show abstract

“…In the closely related kinetoplastid Leishmania two homologues of the DEAD box RNA helicase DED1/DDX3 protein (LeishDED1.1 and LeishDED1.1) form a complex with eIF4G and eIF4E, and have a role in translation initiation (48). We observe that CCR phosphorylation of TbDED1.2 (Tb927.9.12510) at pS48 was up regulated in early G2/M (FCMax 5-fold) at a site not found in TbDED1.1 (Tb927.10.14550), whilst the protein level of TbDED1.2 was unchanged ( Figure 7A).…”

Section: Dynamic Phosphorylation Of Translational Machinerymentioning

confidence: 99%

“…We observe that CCR phosphorylation of TbDED1.2 (Tb927.9.12510) at pS48 was up regulated in early G2/M (FCMax 5-fold) at a site not found in TbDED1.1 (Tb927.10.14550), whilst the protein level of TbDED1.2 was unchanged ( Figure 7A). Since genetic ablation of mRNA by RNA interference (RNAi) results in a strong growth defect for TbDED1.2 but not TbDED1.1 (48), we decided to investigate if ablation of TbDED1.2 resulted in a cell cycle defect. Genetic ablation of TbDED1.2 was performed using tetracycline-inducible RNAi in two independent clones, with induction of RNAi resulting in efficient ablation of mRNA after 24 h and cessation of growth after 48 hours ( Figure 7B).…”

Section: Dynamic Phosphorylation Of Translational Machinerymentioning

confidence: 99%

Organising the cell cycle in the absence of transcriptional control: Dynamic phosphorylation co-ordinates theTrypanosoma bruceicell cycle post-transcriptionally

Benz

Urbaniak

2019

Preprint

View full text Add to dashboard Cite

The cell division cycle of the unicellular eukaryote Trypanosome brucei is tightly regulated despite the paucity of transcriptional control that results from the arrangement of genes in polycistronic units and lack of dynamically regulated transcription factors. To identify the contribution of dynamic phosphorylation to T. brucei cell cycle control we have combined cell cycle synchronisation by centrifugal elutriation with quantitative phosphoproteomic analysis. Cell cycle regulated changes in phosphorylation site abundance (917 sites, average 5-fold change) were more widespread and of a larger magnitude than changes in protein abundance (443 proteins, average 2-fold change) and were mostly independent of each other. Hierarchical clustering of co-regulated phosphorylation sites according to their cell cycle profile revealed that a bulk increase in phosphorylation occurs across the cell cycle, with a significant enrichment of known cell cycle regulators and RNA binding proteins (RBPs) within the largest clusters. Cell cycle regulated changes in essential cell cycle kinases are temporally co-ordinated with differential phosphorylation of components of the kinetochore and eukaryotic initiation factors, along with many RBPs not previously linked to the cell cycle such as eight PSP1-C terminal domain containing proteins. The temporal profiles demonstrate the importance of dynamic phosphorylation in co-ordinating progression through the cell cycle, and provide evidence that RBPs play a central role in post-transcriptional regulation of the T. brucei cell cycle.Data are available via ProteomeXchange with identifier PXD013488.

show abstract

Gene duplication in trypanosomatids – Two DED1 paralogs are functionally redundant and differentially expressed during the life cycle

Cited by 15 publications

References 62 publications

Global proteomic analysis in trypanosomes reveals unique proteins and conserved cellular processes impacted by arginine methylation

Global proteomic analysis in trypanosomes reveals unique proteins and conserved cellular processes impacted by arginine methylation

Trypanosome CNOT10 is essential for the integrity of the NOT deadenylase complex and for degradation of many mRNAs

Organising the cell cycle in the absence of transcriptional control: Dynamic phosphorylation co-ordinates theTrypanosoma bruceicell cycle post-transcriptionally

Contact Info

Product

Resources

About