Identification of core components of the exon junction complex in trypanosomes

Bercovich, Natalia; Levìn, Mariano J.; Clayton, Christine; Vázquez, Martı́n

doi:10.1016/j.molbiopara.2009.03.008

Cited by 19 publications

(38 citation statements)

References 20 publications

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“…However, the RNA helicase UPF-1 that plays a central role clearly originated in the ancestral eukaryote as it is present in excavates and Euglenozoa, as is UPF-2 with which it binds in the nonsense-mediated mRNA decay but as this helicase has multiple functions this does not prove that nonsense-mediated mRNA decay itself arose that early. Nonsense mediated decay is triggered by failure to remove the exon junction complex (EJC) from intron-containing RNA; two of the four EJC proteins are present in trypanosomatids [316], presumably involved in checking trans-splicing (as introns are extremely rare in trypanosomes [317]), so these at least are also ancient.…”

Section: Results: the Origin Of Mitosis And The Nucleusmentioning

confidence: 99%

Origin of the cell nucleus, mitosis and sex: roles of intracellular coevolution

2010

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BackgroundThe transition from prokaryotes to eukaryotes was the most radical change in cell organisation since life began, with the largest ever burst of gene duplication and novelty. According to the coevolutionary theory of eukaryote origins, the fundamental innovations were the concerted origins of the endomembrane system and cytoskeleton, subsequently recruited to form the cell nucleus and coevolving mitotic apparatus, with numerous genetic eukaryotic novelties inevitable consequences of this compartmentation and novel DNA segregation mechanism. Physical and mutational mechanisms of origin of the nucleus are seldom considered beyond the long-standing assumption that it involved wrapping pre-existing endomembranes around chromatin. Discussions on the origin of sex typically overlook its association with protozoan entry into dormant walled cysts and the likely simultaneous coevolutionary, not sequential, origin of mitosis and meiosis.ResultsI elucidate nuclear and mitotic coevolution, explaining the origins of dicer and small centromeric RNAs for positionally controlling centromeric heterochromatin, and how 27 major features of the cell nucleus evolved in four logical stages, making both mechanisms and selective advantages explicit: two initial stages (origin of 30 nm chromatin fibres, enabling DNA compaction; and firmer attachment of endomembranes to heterochromatin) protected DNA and nascent RNA from shearing by novel molecular motors mediating vesicle transport, division, and cytoplasmic motility. Then octagonal nuclear pore complexes (NPCs) arguably evolved from COPII coated vesicle proteins trapped in clumps by Ran GTPase-mediated cisternal fusion that generated the fenestrated nuclear envelope, preventing lethal complete cisternal fusion, and allowing passive protein and RNA exchange. Finally, plugging NPC lumens by an FG-nucleoporin meshwork and adopting karyopherins for nucleocytoplasmic exchange conferred compartmentation advantages. These successive changes took place in naked growing cells, probably as indirect consequences of the origin of phagotrophy. The first eukaryote had 1-2 cilia and also walled resting cysts; I outline how encystation may have promoted the origin of meiotic sex. I also explain why many alternative ideas are inadequate.ConclusionNuclear pore complexes are evolutionary chimaeras of endomembrane- and mitosis-related chromatin-associated proteins. The keys to understanding eukaryogenesis are a proper phylogenetic context and understanding organelle coevolution: how innovations in one cell component caused repercussions on others.ReviewersThis article was reviewed by Anthony Poole, Gáspár Jékely and Eugene Koonin.

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Section: Results: the Origin Of Mitosis And The Nucleusmentioning

confidence: 99%

Origin of the cell nucleus, mitosis and sex: roles of intracellular coevolution

2010

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“…Neither TbSub2 nor the trypanosomal EJC component TbY14 pull down Yra1‐like proteins (B. Schimanski, unpubl. results; Bercovich et al ., ).…”

Section: Discussionmentioning

confidence: 97%

The nuclear mRNA export receptor Mex67‐Mtr2 of Trypanosoma brucei contains a unique and essential zinc finger motif

Dostálová

Käser

Cristodero

et al. 2013

Molecular Microbiology

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SummaryTrypanosoma brucei is the causative agent of Human African Trypanosomiasis. Trypanosomes are early diverged protozoan parasites and show significant differences in their gene expression compared with higher eukaryotes. Due to a lack of individual gene promoters, large polycistronic transcripts are produced and individual mRNAs mature by trans-splicing and polyadenylation. In the absence of transcriptional control, regulation of gene expression occurs posttranscriptionally mainly by control of transcript stability and translation. Regulation of mRNA export from the nucleus to the cytoplasm might be an additional post-transcriptional event involved in gene regulation. However, our knowledge about mRNA export in trypanosomes is very limited. Although export factors of higher eukaryotes are reported to be conserved, only a few orthologues can be readily identified in the genome of T. brucei. Hence, biochemical approaches are needed to identify the export machinery of trypanosomes. Here, we report the functional characterization of the essential mRNA export factor TbMex67. TbMex67 contains a unique and essential N-terminal zinc finger motif. Furthermore, we could identify two interacting export factors namely TbMtr2 and the karyopherin TbIMP1. Our data show that the general heterodimeric export receptor Mex67-Mtr2 is conserved throughout the eukaryotic kingdom albeit exhibiting parasite-specific features.

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“…Any mechanism depending on recognition of the splice junction via the EJC is unlikely. Some of the EJC proteins are present, and form a complex, in trypanosomes [66], though neither binding to the exon junction nor a role in trans splicing have been confirmed. Even assuming that the EJC is deposited at the trans splice junction, it would be stripped off by the scanning small ribosomal subunit complex before translation initiation.…”

Section: Discussionmentioning

confidence: 99%

Is There a Classical Nonsense-Mediated Decay Pathway in Trypanosomes?

et al. 2011

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In many eukaryotes, messenger RNAs with premature termination codons are destroyed by a process called “nonsense-mediated decay”, which requires the RNA helicase Upf1 and also, usually, an interacting factor, Upf2. Recognition of premature termination codons may rely on their distance from either a splice site or the polyadenylation site, and long 3′-untranslated regions can trigger mRNA decay. The protist Trypanosoma brucei relies heavily on mRNA degradation to determine mRNA levels, and 3′-untranslated regions play a major role in control of mRNA decay. We show here that trypanosomes have a homologue of Upf1, TbUPF1, which interacts with TbUPF2 and (in an RNA-dependent fashion) with poly(A) binding protein 1, PABP1. Introduction of a premature termination codon in either an endogenous gene or a reporter gene decreased mRNA abundance, as expected for nonsense-mediated decay, but a dependence of this effect on TbUPF1 could not be demonstrated, and depletion of TbUPF1 by over 95% had no effect on parasite growth or the mRNA transcriptome. Further investigations of the reporter mRNA revealed that increases in open reading frame length tended to increase mRNA abundance. In contrast, inhibition of translation, either using 5′-secondary structures or by lengthening the 5′-untranslated region, usually decreased reporter mRNA abundance. Meanwhile, changing the length of the 3′-untranslated region had no consistent effect on mRNA abundance. We suggest that in trypanosomes, translation per se may inhibit mRNA decay, and interactions with multiple RNA-binding proteins preclude degradation based on 3′-untranslated region length alone.

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Identification of core components of the exon junction complex in trypanosomes

Cited by 19 publications

References 20 publications

Origin of the cell nucleus, mitosis and sex: roles of intracellular coevolution

Origin of the cell nucleus, mitosis and sex: roles of intracellular coevolution

The nuclear mRNA export receptor Mex67‐Mtr2 of Trypanosoma brucei contains a unique and essential zinc finger motif

Is There a Classical Nonsense-Mediated Decay Pathway in Trypanosomes?

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