剪接引导RNA沉默：布氏锥虫中一种新的应激诱导机制。
Spliced-leader RNA silencing: a novel stress-induced mechanism in Trypanosoma brucei.
作者信息
Lustig Yaniv, Sheiner Lilach, Vagima Yaron, Goldshmidt Hanoch, Das Anish, Bellofatto Vivian, Michaeli Shulamit
机构信息
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
出版信息
EMBO Rep. 2007 Apr;8(4):408-13. doi: 10.1038/sj.embor.7400930. Epub 2007 Mar 9.
Abstract
The signal-recognition particle (SRP) mediates the translocation of membrane and secretory proteins across the endoplasmic reticulum upon interaction with the SRP receptor. In trypanosomes, the main RNA molecule is the spliced-leader (SL) RNA, which donates the SL sequence to all messenger RNA through trans-splicing. Here, we show that RNA interference silencing of the SRP receptor (SRalpha) in Trypanosoma brucei caused the accumulation of SRP on ribosomes and triggered silencing of SL RNA (SLS). SLS was elicited due to the failure of the SL RNA-specific transcription factor tSNAP42 to bind to its promoter. SL RNA reduction, in turn, eliminated mRNA processing and resulted in a significant reduction of all mRNA tested. SLS was also induced under pH stress and might function as a master regulator in trypanosomes. SLS is reminiscent of, but distinct from, the unfolded protein response and can potentially act as a new target for parasite eradication.
摘要
信号识别颗粒（SRP）在与SRP受体相互作用时介导膜蛋白和分泌蛋白在内质网上的转运。在锥虫中，主要的RNA分子是剪接前导序列（SL）RNA，它通过反式剪接将SL序列捐赠给所有信使RNA。在这里，我们表明，布氏锥虫中SRP受体（SRalpha）的RNA干扰沉默导致SRP在核糖体上积累，并引发SL RNA（SLS）沉默。SLS是由于SL RNA特异性转录因子tSNAP42未能与其启动子结合而引发的。SL RNA减少反过来消除了mRNA加工，并导致所有测试的mRNA显著减少。在pH胁迫下也会诱导SLS，它可能在锥虫中作为主要调节因子发挥作用。SLS让人联想到但又不同于未折叠蛋白反应，并且有可能成为根除寄生虫的新靶点。
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