Insights into the Regulation of <scp>mRNA</scp> Processing of Polycistronic Transcripts Mediated by <scp>DRBD</scp>4/<scp>PTB</scp>2, a Trypanosome Homolog of the Polypyrimidine Tract‐Binding Protein

Gaudenzi, Javier G. De; Jäger, Adriana V.; Izcovich, Ronan; Campo, Vanina A.

doi:10.1111/jeu.12288

Cited by 13 publications

(15 citation statements)

References 74 publications

(86 reference statements)

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“…It regulates splicing and prevents transsplicing by binding in the regulatory elements present in the intercistronic region (ICR) of the ubp1 and ubp2 genes. These results indicate that TcDRBD4/PTB2 might act by covering the trans-splicing/polyadenylation signals (De Gaudenzi et al, 2016).…”

Section: Rbps With Rrm Domains In T Cruzimentioning

confidence: 82%

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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Section: Rbps With Rrm Domains In T Cruzimentioning

confidence: 82%

RNA Binding Proteins and Gene Expression Regulation in Trypanosoma cruzi

Romagnoli

Holetz

Alves

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Increasing evidence suggests that RBPs can act as multifunctional gene expression regulators (Backlund et al, 2020; De Gaudenzi et al, 2016). Here, we built an in-silico method for the large-scale analysis of RBP-driven regulation using correlation as a proxy for mRNA abundance and translational efficiency (TE) of target genes across 80 human heart samples.…”

Section: Discussionmentioning

confidence: 99%

Multifunctional RNA-binding proteins influence mRNA abundance and translational efficiency of distinct sets of target genes

Schneider-Lunitz

Ruiz-Orera

Hübner

et al. 2021

Preprint

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RNA-binding proteins (RBPs) are key regulators of RNA metabolism. Many RBPs possess uncharacterized RNA-binding domains and localize to multiple subcellular compartments, suggesting their involvement in multiple biological processes. We searched for such multifunctionality within a set of 143 RBPs by integrating experimentally validated target genes with the transcriptomes and translatomes of 80 human hearts. This revealed that RBP abundance is predictive of the extent of target regulation in vivo, leading us to newly associate 27 RBPs with translational control. Amongst those were several splicing factors, of which the muscle specific RBM20 modulated target translation rates through switches in isoform production. For 21 RBPs, we newly observed dual regulatory effects impacting both mRNA levels and translation rates, albeit for virtually independent sets of target genes. We highlight a subset, including G3BP1, PUM1, UCHL5, and DDX3X, where dual regulation is achieved by differential affinity for targets of distinct length and functionality. Strikingly, in a manner very similar to DDX3X, the known splicing factors EFTUD2 and PRPF8 selectively influence target translation rates depending on 5' UTR structure. Our results indicate unanticipated complexity of protein-RNA interactions at consecutive stages of gene expression and implicate multiple core splicing factors as key regulators of translational output.

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“…Indeed, processes like editing and trans -splicing were firstly described in trypanosomatids and later revealed to also occur, in other eukaryotes. However, while in eukaryotes the co-transcriptional RNA processing, surveillance and transport from nucleus to cytoplasm have been widely recognized as regulatory steps in gene expression (Kohler and Hurt, 2007 ), their survey in trypanosomes is very recent (Nazer et al, 2011 , 2012 ; Fadda et al, 2014 ; Antwi et al, 2016 ; De Gaudenzi et al, 2016 ; Kramer et al, 2016 ). Likewise, genome-wide approaches have been used to identify the RNA nature and abundance distribution in the nucleus and the cytoplasm in many eukaryotes (Liao et al, 2010 ; Solnestam et al, 2012 ; Tilgner et al, 2012 ; Zaghlool et al, 2013 ; Bai et al, 2014 ), but such analyses have not yet been reported in trypanosomatids.…”

Section: Discussionmentioning

confidence: 99%

“…The role of the nuclear compartment in the control of the cytoplasmic steady-state transcript levels has been recognized as crucial in eukaryotic gene expression regulation (Kohler and Hurt, 2007 ; Palazzo and Akef, 2012 ) and is also being studied in trypanosomatids (Nazer et al, 2011 , 2012 ; Fadda et al, 2014 ; Antwi et al, 2016 ; De Gaudenzi et al, 2016 ; Kramer et al, 2016 ), for a very recent review see (Clayton, 2016 ). Although specific molecular actors involved in the nucleus-cytoplasmic transport in T. cruzi are being unraveled (Cassola and Frasch, 2009 ; Serpeloni et al, 2011a , b ; Camara Mde et al, 2013 ; Inoue et al, 2014 ), no global analysis of the impact of nuclear compartmentation has been performed yet.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Compartmentalization Contributes to Stage-Specific Gene Expression Control in Trypanosoma cruzi

Pastro

Smircich

Paolo

et al. 2017

Front. Cell Dev. Biol.

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In the protozoan parasite Trypanosoma cruzi, as in other trypanosomatids, transcription of protein coding genes occurs in a constitutive fashion, producing large polycistronic transcription units. These units are composed of non-functionally related genes which are pervasively processed to yield each mRNA. Therefore, post-transcriptional processes are crucial to regulate gene expression. Considering that nuclear compartmentalization could contribute to gene expression regulation, we comparatively studied the nuclear, cytoplasmic and whole cell transcriptomes of the non-infective epimastigote stage of T. cruzi, using RNA-Seq. We found that the cytoplasmic transcriptome tightly correlates with the whole cell transcriptome and both equally correlate with the proteome. Nonetheless, 1,200 transcripts showed differential abundance between the nuclear and cytoplasmic fractions. For the genes with transcript content augmented in the nucleus, significant structural and compositional differences were found. The analysis of the reported epimastigote translatome and proteome, revealed scarce ribosome footprints and encoded proteins for them. Ontology analyses unveiled that many of these genes are distinctive of other parasite life-cycle stages. Finally, the relocalization of transcript abundance in the metacyclic trypomastigote infective stage was confirmed for specific genes. While gene expression is strongly dependent on transcript steady-state level, we here highlight the importance of the distribution of transcripts abundance between compartments in T. cruzi. Particularly, we show that nuclear compartmentation is playing an active role in the developmental stage determination preventing off-stage expression.

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Insights into the Regulation of mRNA Processing of Polycistronic Transcripts Mediated by DRBD4/PTB2, a Trypanosome Homolog of the Polypyrimidine Tract‐Binding Protein

Cited by 13 publications

References 74 publications

RNA Binding Proteins and Gene Expression Regulation in Trypanosoma cruzi

RNA Binding Proteins and Gene Expression Regulation in Trypanosoma cruzi

Multifunctional RNA-binding proteins influence mRNA abundance and translational efficiency of distinct sets of target genes

Nuclear Compartmentalization Contributes to Stage-Specific Gene Expression Control in Trypanosoma cruzi

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