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

The nuclear mRNA export receptor Mex67-Mtr2 of Trypanosoma brucei contains a unique and essential zinc finger motif
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DOI:
10.1111/mmi.12217
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发表时间:
2013-05-01
影响因子:
3.6
通讯作者:
Schimanski, Bernd
Schimanski, Bernd
中科院分区:
生物学2区
文献类型:
--
作者:
Dostalova, Anna;Kaeser, Sandro;Schimanski, Bernd

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布氏锥虫是非洲人类锥虫病的病原体。锥虫是早期分化的原生动物寄生虫,与高等真核生物相比,其基因表达存在显著差异。由于缺乏单个基因启动子,会产生大量多顺反子转录本,并且单个mRNA通过反式剪接和多聚腺苷酸化而成熟。在缺乏转录控制的情况下,基因表达的调控主要在转录后通过控制转录本的稳定性和翻译来进行。mRNA从细胞核输出到细胞质的调控可能是参与基因调控的另一个转录后事件。然而,我们对锥虫mRNA输出的了解非常有限。尽管据报道高等真核生物的输出因子是保守的,但在布氏锥虫的基因组中只能很容易地鉴定出少数直系同源物。因此,需要生物化学方法来鉴定锥虫的输出机制。在此,我们报道了必需的mRNA输出因子TbMex67的功能特性。TbMex67包含一个独特且必需的N末端锌指结构域。此外,我们能够鉴定出两个相互作用的输出因子,即TbMtr2和核转运蛋白TbIMP1。我们的数据表明,通用的异二聚体输出受体Mex67 - Mtr2在整个真核生物界是保守的,尽管表现出寄生虫特异性特征。
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.