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

Trypanosoma 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 post-transcriptionally 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.

Legal Implications of the Use of Export Taxes in Addressing Carbon Leakage: Competing Border Adjustment Measures

The prevailing uncertainties about the future of the post-Kyoto international legal framework for climate mitigation and adaptation increase the likelihood of unilateral trade interventions that aim to address climate policy concerns, as exemplified by the controversial European Union initiative to include the aviation industry in its emissions trading system. The emerging literature suggests that border carbon adjustment (BCA) measures imposed by importing countries would lead to substantial legal complications in relation to World Trade Organization law and hence to possible trade disputes. Lack of legal clarity on BCAs is exacerbated by potential counter or pre-emptive export restrictions that exporting countries might impose on carbon-intensive products. In this context, this paper investigates the interface between legal and welfare implications of competing unilateral BCA measures. It argues that carbon export taxes will be an inevitable part of the future climate change regime in the absence of a multilateral agreement. It also describes the channels through which competing BCAs may lead to trade conflicts and political complications as a result of their distributional and welfare impacts at the domestic and global levels.

Three Shades of Embeddedness, State Capitalism as the Informal Economy, Emic Notions of the Anti-Market, and Counterfeit Garments in the Mauritian Export Processing Zone

Purpose This paper furthers the analysis of patterns regulating capitalist accumulation based on a historical anthropology of economic activities revolving around and within the Mauritian Export Processing Zone (EPZ). Design/methodology/approach This paper uses fieldwork in Mauritius to interrogate and critique two important concepts in contemporary social theory – “embeddedness” and “the informal economy.” These are viewed in the wider frame of social anthropology’s engagement with (neoliberal) capitalism. Findings A process-oriented revision of Polanyi’s work on embeddedness and the “double movement” is proposed to help us situate EPZs within ongoing power struggles found throughout the history of capitalism. This helps us to challenge the notion of economic informality as supplied by Hart and others. Social implications Scholars and policymakers have tended to see economic informality as a force from below, able to disrupt the legal-rational nature of capitalism as practiced from on high. Similarly, there is a view that a precapitalist embeddedness, a “human economy,” has many good things to offer. However, this paper shows that the practices of the state and multinational capitalism, in EPZs and elsewhere, exactly match the practices that are envisioned as the cure to the pitfalls of capitalism. Value of the paper Setting aside the formal-informal distinction in favor of a process-oriented analysis of embeddedness allows us better to understand the shifting struggles among the state, capital, and labor.

CTIF is involved in mRNA export in human cells

In eukaryotic cells, translation of messenger RNA (mRNA) can be initiated either on transcripts associated with the cap-binding complex (CBC; consisting of CBP80 and CBP20) or on transcripts with the eukaryotic translation initiation factor (eIF) 4E bound to the cap. Together with eIF4G and eIF4A, eIF4E forms the eIF4F-complex, which mediates translation initiation during the bulk of cellular protein synthesis. Functionally substituting for eIF4G, the CBP80/20-dependent translation initiation factor (CTIF) has been reported to be part of the CBC-dependent translation initiation complex 1,2. CTIF consists of a N-terminal CBP80-binding domain and a conserved C-terminal MIF4G domain 1. This MIF4G domain has been shown to mediate the interaction between CTIF and different factors such as eIF3g and the stem-loop binding protein (SLBP) 2,3. Here we provide evidence that CTIF, besides its function in translation initiation, is also involved in mRNA translocation from the nucleus to the cytoplasm, possibly through a direct interaction with the nuclear export factor NFX1/TAP. Taken together our results suggest that CTIF can function as a platform that interacts with proteins involved in different steps of the mRNA metabolism.

CTIF is involved in mRNA export in human cells

In eukaryotic cells translation initiation of messenger RNA (mRNA) transcripts can be initiated either by the cap-binding complex (CBC) consisting of CBP80 and CBP20, or by the eukaryotic translation initiation factor (eIF) 4E. Together with eIF4G and eIF4A, eIF4E forms the eIF4F-complex, which mediates initiation of the bulk of cellular translation. Analogous to eIF4G, the CBP80/20-dependent translation initiation factor (CTIF) has been reported to be part of the CBC-dependent translation initiation complex. CTIF consists of a N-terminal CBP80-binding domain and a conserved C-terminal MIF4G domain. This MIF4G domain has been shown to mediate the interaction between CTIF and different factors such as eIF3g and the stem-loop binding protein (SLBP). Here we show data indicating that CTIF, besides its function in translation initiation, is involved in mRNA translocation from the nucleus to the cytoplasm, possibly through a direct interaction with the nuclear export factor NFX1/TAP. Taken together our results suggest that CTIF can function as a platform that interacts with proteins involved in different steps of mRNA metabolism.

CTIF is involved in mRNA export in human cells

In eukaryotic cells translation initiation of messenger RNA (mRNA) transcripts can be initiated either by the cap-binding complex (CBC) consisting of CBP80 and CBP20, or by the eukaryotic translation initiation factor (eIF) 4E. Together with eIF4G and eIF4A, eIF4E forms the eIF4F-complex, which mediates translation initiation during the bulk of cellular protein synthesis [1,2]. Functionally analogous to eIF4G, the CBP80/20-dependent translation initiation factor (CTIF) has been reported to be part of the CBC-dependent translation initiation complex [3,4]. CTIF consists of a N-terminal CBP80-binding domain and a conserved C-terminal MIF4G domain [3]. This MIF4G domain has been shown to mediate the interaction between CTIF and different factors such as eIF3g and the stem-loop binding protein (SLBP) [4,5]. Here we show data indicating that CTIF, besides its function in translation initiation, is involved in mRNA translocation from the nucleus to the cytoplasm, possibly through a direct interaction with the nuclear export factor NFX1/TAP. Taken together our results suggest that CTIF can function as a platform that interacts with proteins involved in different steps of the mRNA metabolism. [1] Haghighat A. and Sonenberg N. (1997) JBC 272:21677-21680 [2] Gross J.D. et al. (2003) Cell 115:739-750 [3] Kim K.M. et al. (2009) Genes Dev 23:2033-2045 [4] Choe J. et al. (2012) JBC 287:18500-18509 [5] Choe J. et al. (2013) NAR 41:1307-1318

NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway

Trypanosomes mostly regulate gene expression through post-transcriptional mechanisms, particularly mRNA stability. However, much mRNA degradation is cytoplasmic such that mRNA nuclear export must represent an important level of regulation. Ribosomal RNAs must also be exported from the nucleus and the trypanosome orthologue of NMD3 has been confirmed to be involved in rRNA processing and export, matching its function in other organisms. Surprisingly, we found that TbNMD3 depletion also generates mRNA accumulation of procyclin-associated genes (PAGs), these being co-transcribed by RNA polymerase I with the procyclin surface antigen genes expressed on trypanosome insect forms. By whole transcriptome RNA-seq analysis of TbNMD3-depleted cells we confirm the regulation of the PAG transcripts by TbNMD3 and using reporter constructs reveal that PAG1 regulation is mediated by its 5'UTR. Dissection of the mechanism of regulation demonstrates that it is not dependent upon translational inhibition mediated by TbNMD3 depletion nor enhanced transcription. However, depletion of the nuclear export factors XPO1 or MEX67 recapitulates the effects of TbNMD3 depletion on PAG mRNAs and mRNAs accumulated in the nucleus of TbNMD3-depleted cells. These results invoke a novel RNA regulatory mechanism involving the NMD3-dependent nuclear export of mRNA cargos, suggesting a shared platform for mRNA and rRNA export.