Coordinated gene expression by post-transcriptional regulons in African trypanosomes

Ouellette, Marc; Papadopoulou, Barbara

doi:10.1186/jbiol203

Cited by 52 publications

(57 citation statements)

References 13 publications

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“…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%

“…The ability to bind eIF4G can be negated by 4E-binding proteins Richter and Sonenberg 2005), and binding activity is implicated in the selective translation of RNA subgroups designated "regulons" (Culjkovic et al 2007;Keene 2007). The existence of coordinated mRNA regulons is supported in the kinetoplastid protozoa (Ouellette and Papadopoulou 2009;Queiroz et al 2009;Das et al 2012;De Gaudenzi et al 2013), however their mechanism of cap-mediated translation regulation remains a mystery.…”

Section: Introductionmentioning

confidence: 99%

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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

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

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

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“…As a consequence of their ''strange'' gene organization, post-transcriptional processes, especially mRNA degradation, are exceptionally important in the control of Kinetoplastid gene expression (for review, see Clayton and Shapira 2007;Ouellette and Papadopoulou 2009;Fernández-Moya and Estévez 2010;Kramer and Carrington 2011). Trypanosomes are therefore an ideal model system for the analysis of mRNA turnover.…”

Section: Introductionmentioning

confidence: 99%

The role of the 5′–3′ exoribonuclease XRNA in transcriptome-wide mRNA degradation

Manful¹,

Fadda

Clayton

2011

RNA

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The steady-state level of each mRNA in a cell is a balance between synthesis and degradation. Here, we use high-throughput RNA sequencing (RNASeq) to determine the relationship between mRNA degradation and mRNA abundance on a transcriptome-wide scale. The model organism used was the bloodstream form of Trypanosoma brucei, a protist that lacks regulation of RNA polymerase II initiation. The mRNA half-lives varied over two orders of magnitude, with a median half-life of 13 min for total (rRNA-depleted) mRNA. Data for poly(A)+ RNA yielded shorter half-lives than for total RNA, indicating that removal of the poly(A) tail was usually the first step in degradation. Depletion of the major 59-39 exoribonuclease, XRNA, resulted in the stabilization of most mRNAs with half-lives under 30 min. Thus, on a transcriptome-wide scale, degradation of most mRNAs is initiated by deadenylation. Trypanosome mRNA levels are strongly influenced by gene copy number and mRNA half-life: Very abundant mRNAs that are required throughout the life-cycle may be encoded by multicopy genes and have intermediate-to-long half-lives; those encoding ribosomal proteins, with one to two gene copies, are exceptionally stable. Developmentally regulated transcripts with a lower abundance in the bloodstream forms than the procyclic forms had half-lives around the median, whereas those with a higher abundance in the bloodstream forms than the procyclic forms, such as those encoding glycolytic enzymes, had longer half-lives.

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“…has been discussed previously (17, 46 -51), it has been pointed out that searches for shared motifs in clusters of co-regulated genes in T. brucei met with limited success (17). Our work shows that these shared motifs exist in T. cruzi and suggests the presence of functional post-transcriptional regulons in these parasites.…”

Section: Discussionmentioning

confidence: 67%

“…The existence of these post-transcriptional regulons would be a very appropriate mechanism for the developmental regulation of gene expression in trypanosomatids. However, searches for shared motifs in clusters of co-regulated genes in trypanosomatids have met with limited success (17). In this regard, a common mechanism of stage-regulated expression of at least 85 genes mediated by a conserved 3Ј-UTR 450-nt ciselement has been proposed in Leishmania major (18).…”

mentioning

confidence: 99%

A 43-Nucleotide U-rich Element in 3′-Untranslated Region of Large Number of Trypanosoma cruzi Transcripts Is Important for mRNA Abundance in Intracellular Amastigotes

Gaudenzi

Álvarez

et al. 2012

Journal of Biological Chemistry

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Background: Trypanosoma cruzi regulates gene expression by means of post-transcriptional mechanisms. Results: A 43-nt U-rich element was found in the 3Ј-UTR of a large number of mRNAs that are more abundant in intracellular amastigotes. Conclusion:The 43-nt U-rich element might be involved in the modulation of abundance and/or translation of transcripts in amastigotes. Significance: Results suggest the existence of stage-specific RNA regulons in T. cruzi.

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Coordinated gene expression by post-transcriptional regulons in African trypanosomes

Cited by 52 publications

References 13 publications

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

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

The role of the 5′–3′ exoribonuclease XRNA in transcriptome-wide mRNA degradation

A 43-Nucleotide U-rich Element in 3′-Untranslated Region of Large Number of Trypanosoma cruzi Transcripts Is Important for mRNA Abundance in Intracellular Amastigotes

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