Alterations in DRBD3 Ribonucleoprotein Complexes in Response to Stress in Trypanosoma brucei

Fernández‐Moya, Sandra M.; García‐Pérez, Angélica; Krämer, Susanne; Carrington, Mark; Estévez, Antonio M.

doi:10.1371/journal.pone.0048870

Cited by 41 publications

(37 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Taken together, these findings indicate that Tc DRBD4/PTB2 is excluded from polysomes, as previously reported for T. brucei DRBD3 (Fernandez‐Moya et al. ), and suggest that Tc DRBD4/PTB2‐containing RNP complexes are not involved in translation events.…”

Section: Resultssupporting

confidence: 89%

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

Gaudenzi

Jäger

Izcovich

et al. 2016

J Eukaryotic Microbiology

View full text Add to dashboard Cite

Trypanosomes regulate gene expression mostly by posttranscriptional mechanisms, including control of mRNA turnover and translation efficiency. This regulation is carried out via certain elements located at the 3'-untranslated regions of mRNAs, which are recognized by RNA-binding proteins. In trypanosomes, trans-splicing is of central importance to control mRNA maturation. We have previously shown that TcDRBD4/PTB2, a trypanosome homolog of the human polypyrimidine tract-binding protein splicing regulator, interacts with the intergenic region of one specific dicistronic transcript, referred to as TcUBP (and encoding for TcUBP1 and TcUBP2, two closely kinetoplastid-specific proteins). In this work, a survey of TcUBP RNA processing revealed certain TcDRBD4/PTB2-regulatory elements within its intercistronic region, which are likely to influence the trans-splicing rate of monocistronic-derived transcripts. Furthermore, TcDRBD4/PTB2 overexpression in epimastigote cells notably decreased both UBP1 and UBP2 protein expression. This type of posttranscriptional gene regulatory mechanism could be extended to other transcripts as well, as we identified several other RNA precursor molecules that specifically bind to TcDRBD4/PTB2. Altogether, these findings support a model in which TcDRBD4/PTB2-containing ribonucleoprotein complexes can prevent trans-splicing. This could represent another stage of gene expression regulation mediated by the masking of trans-splicing/polyadenylation signals.

show abstract

Section: Resultssupporting

confidence: 89%

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

Gaudenzi

Jäger

Izcovich

et al. 2016

J Eukaryotic Microbiology

View full text Add to dashboard Cite

show abstract

“…The concept of RNA regulons, multiple mRNAs with a shared functional relationship, has been implicated in kinetoplastids (Zick et al 2005;Estévez 2008;Ouellette and Papadopoulou 2009;Queiroz et al 2009;Fernandez-Moya et al 2012). Notably, mammalian eIF4E is a central protein in an RNA regulon related to mRNA export and cell proliferation (Culjkovic et al 2005;Culjkovic et al 2006).…”

Section: Discussionmentioning

confidence: 99%

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

Freire

Vashisht

Malvezzi

et al. 2014

RNA

View full text Add to dashboard Cite

Members of the eIF4E mRNA cap-binding family are involved in translation and the modulation of transcript availability in other systems as part of a three-component complex including eIF4G and eIF4A. The kinetoplastids possess four described eIF4E and five eIF4G homologs. We have identified two new eIF4E family proteins in Trypanosoma brucei, and define distinct complexes associated with the fifth member, TbEIF4E5. The cytosolic TbEIF4E5 protein binds cap 0 in vitro. TbEIF4E5 was found in association with two of the five TbEIF4Gs. TbIF4EG1 bound TbEIF4E5, a 47.5-kDa protein with two RNA-binding domains, and either the regulatory protein 14-3-3 II or a 117.5-kDa protein with guanylyltransferase and methyltransferase domains in a potentially dynamic interaction. The TbEIF4G2/TbEIF4E5 complex was associated with a 17.9-kDa hypothetical protein and both 14-3-3 variants I and II. Knockdown of TbEIF4E5 resulted in the loss of productive cell movement, as evidenced by the inability of the cells to remain in suspension in liquid culture and the loss of social motility on semisolid plating medium, as well as a minor reduction of translation. Cells appeared lethargic, as opposed to compromised in flagellar function per se. The minimal use of transcriptional control in kinetoplastids requires these organisms to implement downstream mechanisms to regulate gene expression, and the TbEIF4E5/TbEIF4G1/117.5-kDa complex in particular may be a key player in that process. We suggest that a pathway involved in cell motility is affected, directly or indirectly, by one of the TbEIF4E5 complexes.

show abstract

“…Several clusters of stress regulated transcripts were observed (as depicted in Table 5), denoting that potential RNA regulons can still coordinate gene expression under osmotic stress conditions. In this context, it was also shown that TbDRBD3 remains bound to its specific target transcripts after starvation or arsenite treatment (Fernandez-Moya et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of 3′-untranslated regions supports the existence of post-transcriptional regulons controlling gene expression in trypanosomes

Gaudenzi

Carmona

Agüero

et al. 2013

PeerJ

View full text Add to dashboard Cite

In eukaryotic cells, a group of messenger ribonucleic acids (mRNAs) encoding functionally interrelated proteins together with the trans-acting factors that coordinately modulate their expression is termed a post-transcriptional regulon, due to their partial analogy to a prokaryotic polycistron. This mRNA clustering is organized by sequence-specific RNA-binding proteins (RBPs) that bind cis-regulatory elements in the noncoding regions of genes, and mediates the synchronized control of their fate. These recognition motifs are often characterized by conserved sequences and/or RNA structures, and it is likely that various classes of cis-elements remain undiscovered. Current evidence suggests that RNA regulons govern gene expression in trypanosomes, unicellular parasites which mainly use post-transcriptional mechanisms to control protein synthesis. In this study, we used motif discovery tools to test whether groups of functionally related trypanosomatid genes contain a common cis-regulatory element. We obtained conserved structured RNA motifs statistically enriched in the noncoding region of 38 out of 53 groups of metabolically related transcripts in comparison with a random control. These motifs have a hairpin loop structure, a preferred sense orientation and are located in close proximity to the open reading frames. We found that 15 out of these 38 groups represent unique motifs in which most 3′-UTR signature elements were group-specific. Two extensively studied Trypanosoma cruzi RBPs, TcUBP1 and TcRBP3 were found associated with a few candidate RNA regulons. Interestingly, 13 motifs showed a strong correlation with clusters of developmentally co-expressed genes and six RNA elements were enriched in gene clusters affected after hyperosmotic stress. Here we report a systematic genome-wide in silico screen to search for novel RNA-binding sites in transcripts, and describe an organized network of several coordinately regulated cohorts of mRNAs in T. cruzi. Moreover, we found that structured RNA elements are also conserved in other human pathogens. These results support a model of regulation of gene expression by multiple post-transcriptional regulons in trypanosomes.

show abstract

Alterations in DRBD3 Ribonucleoprotein Complexes in Response to Stress in Trypanosoma brucei

Cited by 41 publications

References 35 publications

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

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

eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei

Genome-wide analysis of 3′-untranslated regions supports the existence of post-transcriptional regulons controlling gene expression in trypanosomes

Contact Info

Product

Resources

About