The RNA-binding protein TbDRBD3 regulates the stability of a specific subset of mRNAs in trypanosomes

The RNA-binding protein TbDRBD3 regulates the stability of a specific subset of mRNAs in trypanosomes
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DOI:
10.1093/nar/gkn406
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发表时间:
2008-08-01
影响因子:
14.9
通讯作者:
Estevez, Antonio M.
Estevez, Antonio M.
中科院分区:
生物学2区
文献类型:
--
作者:
Estevez, Antonio M.

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在锥虫中,RNA聚合酶II依赖性转录起始的调节明显缺乏,这对理解这些真核生物如何调节基因表达以适应它们在生命周期中发现的对比环境提出了挑战。到目前为止的证据表明,mRNA周转和翻译的主要控制点,其中的监管是在锥虫。然而,人们对哪些蛋白质参与其中以及它们如何调节不同生命阶段不同mRNA的丰度和翻译知之甚少。在这项工作中,一个RNA结合蛋白,TbDRBD 3,已被确定的亲和层析,其功能解决使用RNA干扰,微阵列分析和免疫沉淀的mRNA-蛋白质复合物。获得的结果表明,TbDRBD 3结合到一个子集的发育调控的mRNA编码膜蛋白,这种协会促进稳定的目标转录。这些观察提高了TbDRBD 3-mRNA复合物作为转录后操纵子的可能性,并提供了一个框架来解释锥虫如何在没有转录控制的情况下调节基因表达。
In trypanosomes, the apparent lack of regulation of RNA polymerase II-dependent transcription initiation poses a challenge to understand how these eukaryotes adjust gene expression to adapt to the contrasting environments they find during their life cycles. Evidence so far indicates that mRNA turnover and translation are the major control points in which regulation is exerted in trypanosomes. However, very little is known about which proteins are involved, and how do they regulate the abundance and translation of different mRNAs in different life stages. In this work, an RNA-binding protein, TbDRBD3, has been identified by affinity chromatography, and its function addressed using RNA interference, microarray analysis and immunoprecipitation of mRNA-protein complexes. The results obtained indicate that TbDRBD3 binds to a subset of developmentally regulated mRNAs encoding membrane proteins, and that this association promotes the stabilization of the target transcripts. These observations raise the possibility that TbDRBD3-mRNA complexes act as a post-transcriptional operon, and provide a framework to interpret how trypanosomes regulate gene expression in the absence of transcriptional control.