Puf Mediates Translation Repression of Transmission-Blocking Vaccine Candidates in Malaria Parasites
Puf Mediates Translation Repression of Transmission-Blocking Vaccine Candidates in Malaria Parasites
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DOI：
10.1371/journal.ppat.1003268
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发表时间：
2013-04-01
期刊：
影响因子：
6.7
通讯作者：
Cui, Liwang
中科院分区：
文献类型：
--
作者：
Miao, Jun;Fan, Qi;Cui, Liwang
基因表达的翻译控制在发育中起着至关重要的作用。在疟疾寄生虫中，在脊椎动物宿主和蚊子媒介之间的特化过渡阶段的发展期间，翻译调节是至关重要的。在这里，我们表明，一个Pumilio/FBF（Puf）家族RNA结合蛋白，PfPuf 2，需要翻译抑制的配子体中的一些转录本，包括两个基因编码的传输阻断疫苗候选人Pfs 25和Pfs 28。尽管迄今为止的研究支持通过靶mRNA的3'非翻译区（UTR）的Puf介导的翻译调节的范例，但本研究首次在pfs 25的5' UTR中鉴定了功能性Puf结合元件（PBE）。我们提供了体外和体内证据来证明PfPuf 2结合pfs 25和pfs 28中的PBE以介导翻译抑制。这一发现为Pufs作为多功能翻译调节因子提供了新的观点，并揭示了它们在真核生物低级分支发育中的功能。
Translational control of gene expression plays an essential role in development. In malaria parasites, translational regulation is critical during the development of specialized transition stages between the vertebrate host and mosquito vector. Here we show that a Pumilio/FBF (Puf) family RNA-binding protein, PfPuf2, is required for the translation repression of a number of transcripts in gametocytes including two genes encoding the transmission-blocking vaccine candidates Pfs25 and Pfs28. Whereas studies to date support a paradigm of Puf-mediated translation regulation through 3' untranslated regions (UTRs) of target mRNAs, this study, for the first time, identifies a functional Puf-binding element (PBE) in the 5'UTR of pfs25. We provide both in vitro and in vivo evidence to demonstrate that PfPuf2 binds to the PBEs in pfs25 and pfs28 to mediate translation repression. This finding provides a renewed view of Pufs as versatile translation regulators and sheds light on their functions in the development of lower branches of eukaryotes.