A novel Plasmodium falciparum SR protein is an alternative splicing factor required for the parasites' proliferation in human erythrocytes.

A novel Plasmodium falciparum SR protein is an alternative splicing factor required for the parasites' proliferation in human erythrocytes.
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DOI:
10.1093/nar/gks735
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发表时间:
2012-10
影响因子:
14.9
通讯作者:
Dzikowski R
Dzikowski R
中科院分区:
生物学2区
文献类型:
--
作者:
Eshar S;Allemand E;Sebag A;Glaser F;Muchardt C;Mandel-Gutfreund Y;Karni R;Dzikowski R

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疟疾寄生虫有一个复杂的生命周期,在此期间,它们经历了重大的生物变化,以适应不同的宿主和不断变化的环境。恶性疟原虫是造成人类最致命疟疾的物种,它以相对较少的基因维持着这种复杂的生命周期。选择性剪接(AS)是一种重要的转录后机制,它使真核生物能够从相对较少的基因中扩增出其蛋白质库。SR蛋白是高等真核生物中AS的主要调节蛋白。然而,剪接的调节以及疟原虫属的AS机制。仍然难以捉摸在这里,我们表明PfSR 1,一个假定的恶性疟原虫SR蛋白,可以在体外介导RNA剪接。此外,我们表明PfSR 1作为AS因子在体内系统中的小基因类似于哺乳动物SR蛋白SRSF 1。PfSR 1-myc在恶性疟原虫中的表达在红细胞内发育过程中显示出不同的细胞定位模式。此外,我们确定PfSR 1的预测RS域是必不可少的,其本地化的核。最后,我们证明了pfsr 1的适当调节是人体红细胞中寄生虫增殖所必需的,并且pfsr 1的过表达影响了体内恶性疟原虫基因的AS活性。
Malaria parasites have a complex life cycle, during which they undergo significant biological changes to adapt to different hosts and changing environments. Plasmodium falciparum, the species responsible for the deadliest form of human malaria, maintains this complex life cycle with a relatively small number of genes. Alternative splicing (AS) is an important post-transcriptional mechanisms that enables eukaryotic organisms to expand their protein repertoire out of relatively small number of genes. SR proteins are major regulators of AS in higher eukaryotes. Nevertheless, the regulation of splicing as well as the AS machinery in Plasmodium spp. are still elusive. Here, we show that PfSR1, a putative P. falciparum SR protein, can mediate RNA splicing in vitro. In addition, we show that PfSR1 functions as an AS factor in mini-gene in vivo systems similar to the mammalian SR protein SRSF1. Expression of PfSR1-myc in P. falciparum shows distinct patterns of cellular localization during intra erythrocytic development. Furthermore, we determine that the predicted RS domain of PfSR1 is essential for its localization to the nucleus. Finally, we demonstrate that proper regulation of pfsr1 is required for parasite proliferation in human RBCs and over-expression of pfsr1 influences AS activity of P. falciparum genes in vivo.
旋钮阳性和旋钮阴性疟原虫恶性疟原虫在感染红细胞表面的菌株特异性疟疾抗原的表达上有所不同。
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发表时间: 1984-11-01
影响因子: 15.3
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发表时间: 2008-10-03
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发表时间: 1994-09-16
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