The DRBD13 RNA binding protein is involved in the insect‐stage differentiation process of <i>Trypanosoma brucei</i>

Jha, Bhaskar Anand; Gazestani, Vahid H.; Yip, Chun Wai; Salavati, Reza

doi:10.1016/j.febslet.2015.05.036

Cited by 25 publications

(25 citation statements)

References 36 publications

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“…We found that cells over‐expressing the (ARE)‐regulating protein DRBD13, is also disadvantageous for cell growth. DRBD13 down‐regulates transcripts encoding cell surface coat proteins (Jha et al ., ). Although the effect of over‐expressing DRBD13 in bloodstream forms has not been evaluated, DRBD13 levels are tightly regulated in the procyclic stage, as both DRBD13 over‐expression and depletion were deleterious to the parasite's growth.…”

Section: Resultsmentioning

confidence: 97%

Gene expression regulatory networks in Trypanosoma brucei: insights into the role of the mRNA‐binding proteome

Lueong

Merce

Fischer

et al. 2016

Molecular Microbiology

113

206

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Control of gene expression at the post-transcriptional level is essential in all organisms, and RNA-binding proteins play critical roles from mRNA synthesis to decay. To fully understand this process, it is necessary to identify the complete set of RNA-binding proteins and the functional consequences of the protein-mRNA interactions. Here, we provide an overview of the proteins that bind to mRNAs and their functions in the pathogenic bloodstream form of Trypanosoma brucei. We describe the production of a small collection of open-reading frames encoding proteins potentially involved in mRNA metabolism. With this ORFeome collection, we used tethering to screen for proteins that play a role in post-transcriptional control. A yeast two-hybrid screen showed that several of the discovered repressors interact with components of the CAF1/NOT1 deadenylation complex. To identify the RNA-binding proteins, we obtained the mRNA-bound proteome. We identified 155 high-confidence candidates, including many not previously annotated as RNA-binding proteins. Twenty seven of these proteins affected reporter expression in the tethering screen. Our study provides novel insights into the potential trypanosome mRNPs composition, architecture and function.

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Section: Resultsmentioning

confidence: 97%

Gene expression regulatory networks in Trypanosoma brucei: insights into the role of the mRNA‐binding proteome

Lueong

Merce

Fischer

et al. 2016

Molecular Microbiology

113

206

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“…However, due to the limitations of this methodology, only one group reported success in knocking out RBPs with this approach (Alcantara et al, 2018). Accordingly, this approach is not feasible in cases where the target gene is essential, which seems to be the case for many RBPs, as reported in T. brucei through gene silencing assays (Das et al, 2012;Wurst et al, 2012;Droll et al, 2013;Fernández-Moya et al, 2014;Jha et al, 2015;Levy et al, 2015).…”

Section: Knockout Of Rbp Genesmentioning

confidence: 99%

RNA Binding Proteins and Gene Expression Regulation in Trypanosoma cruzi

Romagnoli

Holetz

Alves

et al. 2020

Front. Cell. Infect. Microbiol.

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The regulation of gene expression in trypanosomatids occurs mainly at the post-transcriptional level. In the case of Trypanosoma cruzi, the characterization of messenger ribonucleoprotein (mRNP) particles has allowed the identification of several classes of RNA binding proteins (RBPs), as well as non-canonical RBPs, associated with mRNA molecules. The protein composition of the mRNPs as well as the localization and functionality of the mRNAs depend on their associated proteins. mRNPs can also be organized into larger complexes forming RNA granules, which function as stress granules or P-bodies depending on the associated proteins. The fate of mRNAs in the cell, and consequently the genes expressed, depends on the set of proteins associated with the messenger molecule. These proteins allow the coordinated expression of mRNAs encoding proteins that are related in function, resulting in the formation of post-transcriptional operons. However, the puzzle posed by the combinatorial association of sets of RBPs with mRNAs and how this relates to the expressed genes remain to be elucidated. One important tool in this endeavor is the use of the CRISPR/CAS system to delete genes encoding RBPs, allowing the evaluation of their effect on the formation of mRNP complexes and associated mRNAs in the different compartments of the translation machinery. Accordingly, we recently established this methodology for T. cruzi and deleted the genes encoding RBPs containing zinc finger domains. In this manuscript, we will discuss the data obtained and the potential of the CRISPR/CAS methodology to unveil the role of RBPs in T. cruzi gene expression regulation.

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“…DRBD3, a protein containing two RRM domains, plays a role both in splicing and mRNA stability in T. brucei (Estévez 2008;Das et al 2012). Also, DRBD13 has been demonstrated to negatively regulate mRNAs encoding for cell membrane-associated proteins via interaction with AREs of the target transcripts (Jha et al 2015). More recently, we showed that the Leishmania infantum Alba3 protein can stabilize the developmentally regulated amastin transcripts specifically in the amastigote stage upon binding to a U-rich element in the 3 ′ UTR (Dupé et al 2014).…”

Section: Introductionmentioning

confidence: 96%

The Pumilio-domain protein PUF6 contributes to SIDER2 retroposon-mediated mRNA decay in Leishmania

Azizi

Dumas

Papadopoulou

2017

RNA

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Leishmania and other trypanosomatid protozoa lack control at the level of transcription initiation and regulate gene expression exclusively post-transcriptionally. We have reported previously that Leishmania harbors a unique class of short interspersed degenerate retroposons (SIDERs) that are predominantly located within 3 ′ ′ ′ ′ ′ UTRs and play a major role in post-transcriptional control. We have shown that members of the SIDER2 subfamily initiate mRNA decay through endonucleolytic cleavage within the second conserved 79-nt signature sequence of SIDER2 retroposons. Here, we have developed an optimized MS2 coat protein tethering system to capture trans-acting factor(s) regulating SIDER2-mediated mRNA decay. Tethering of the MS2 coat protein to a reporter RNA harboring two MS2 stem-loop aptamers and the cognate SIDER2-containing 3 ′ ′ ′ ′ ′ UTR in combination with immunoprecipitation and mass spectrometry analysis led to the identification of RNA-binding proteins with known functions in mRNA decay. Among the candidate SIDER2-interacting proteins that were individually tethered to a SIDER2 reporter RNA, the Pumilio-domain protein PUF6 was shown to enhance degradation and reduce transcript half-life. Furthermore, we showed that PUF6 binds to SIDER2 sequences that include the regulatory 79-nt signature motif, hence contributing to the mRNA decay process. Consistent with a role of PUF6 in SIDER2-mediated decay, genetic inactivation of PUF6 resulted in increased accumulation and higher stability of endogenous SIDER2-bearing transcripts. Overall, these studies provide new insights into regulated mRNA decay pathways in Leishmania controlled by SIDER2 retroposons and propose a broader role for PUF proteins in mRNA decay within the eukaryotic kingdom.

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The DRBD13 RNA binding protein is involved in the insect‐stage differentiation process of Trypanosoma brucei

Cited by 25 publications

References 36 publications

Gene expression regulatory networks in Trypanosoma brucei: insights into the role of the mRNA‐binding proteome

Gene expression regulatory networks in Trypanosoma brucei: insights into the role of the mRNA‐binding proteome

RNA Binding Proteins and Gene Expression Regulation in Trypanosoma cruzi

The Pumilio-domain protein PUF6 contributes to SIDER2 retroposon-mediated mRNA decay in Leishmania

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