Integrative analysis of the Trypanosoma brucei gene expression cascade predicts differential regulation of mRNA processing and unusual control of ribosomal protein expression.
Integrative analysis of the Trypanosoma brucei gene expression cascade predicts differential regulation of mRNA processing and unusual control of ribosomal protein expression.
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DOI：
10.1186/s12864-016-2624-3
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发表时间：
2016-04-26
期刊：
影响因子：
4.4
通讯作者：
Clayton C
中科院分区：
文献类型：
--
作者：
Antwi EB;Haanstra JR;Ramasamy G;Jensen B;Droll D;Rojas F;Minia I;Terrao M;Mercé C;Matthews K;Myler PJ;Parsons M;Clayton C
布鲁氏锥虫是一种单细胞寄生虫，在哺乳动物(血流形式)和采采蝇(原环状形式)中繁殖。锥虫RNA聚合酶II的转录是多顺反子的，单个的mRNAs通过反式剪接和聚腺苷酸化被切除。我们之前对血流和原周期形式的mRNA半衰期进行了详细的测量，并开发了血流形式的基因表达的数学模型。在整个转录组水平上，许多血流形式的mRNAs没有模型预测的那么丰富。我们改进了已发表的数学模型，并将其推广到原循环形式。我们使用该模型和已知的信使核糖核酸半衰期来预测单个信使核糖核酸的丰度，假设快速、不受调控的信使核糖核酸处理；然后我们将结果与测量的信使核糖核酸丰度进行比较。值得注意的是，该模型很好地预测了大多数原环形式的mRNAs的丰度，这在很大程度上是由mRNAs衰减率和长度的变化解释的。在血流形式中，更多的mRNAs没有预期的丰富。我们列出了可能表现出特别缓慢或低效处理的mRNA，无论是在这两种形式中，还是在发育调控下。我们还测量了在相同条件下生长的锥虫体内所有mRNAs的核糖体占有率，用于测量mRNA周转率。在原环型中，核糖体密度与mRNA半衰期呈弱正相关，提示翻译与mRNA衰变之间存在串扰；核糖体密度与多聚体上mRNA的比例相关，表明翻译起始受到控制。原周期中的核糖体蛋白mRNAs似乎被异常迅速地处理，但翻译得很差。原环状锥体中的mRNAs水平主要由长度和mRNA衰变决定，并有一定的前体加工控制。在血流形式中，核事件的变化在转录组调节中起着更大的作用，这表明在适应哺乳动物寄生的过程中获得了新的控制机制。本文的在线版本(doi：10.1186/s12864-0162624-3)包含补充材料，授权用户可以使用。
Trypanosoma brucei is a unicellular parasite which multiplies in mammals (bloodstream form) and Tsetse flies (procyclic form). Trypanosome RNA polymerase II transcription is polycistronic, individual mRNAs being excised by trans splicing and polyadenylation. We previously made detailed measurements of mRNA half-lives in bloodstream and procyclic forms, and developed a mathematical model of gene expression for bloodstream forms. At the whole transcriptome level, many bloodstream-form mRNAs were less abundant than was predicted by the model. We refined the published mathematical model and extended it to the procyclic form. We used the model, together with known mRNA half-lives, to predict the abundances of individual mRNAs, assuming rapid, unregulated mRNA processing; then we compared the results with measured mRNA abundances. Remarkably, the abundances of most mRNAs in procyclic forms are predicted quite well by the model, being largely explained by variations in mRNA decay rates and length. In bloodstream forms substantially more mRNAs are less abundant than predicted. We list mRNAs that are likely to show particularly slow or inefficient processing, either in both forms or with developmental regulation. We also measured ribosome occupancies of all mRNAs in trypanosomes grown in the same conditions as were used to measure mRNA turnover. In procyclic forms there was a weak positive correlation between ribosome density and mRNA half-life, suggesting cross-talk between translation and mRNA decay; ribosome density was related to the proportion of the mRNA on polysomes, indicating control of translation initiation. Ribosomal protein mRNAs in procyclics appeared to be exceptionally rapidly processed but poorly translated. Levels of mRNAs in procyclic form trypanosomes are determined mainly by length and mRNA decay, with some control of precursor processing. In bloodstream forms variations in nuclear events play a larger role in transcriptome regulation, suggesting aquisition of new control mechanisms during adaptation to mammalian parasitism. The online version of this article (doi:10.1186/s12864-016-2624-3) contains supplementary material, which is available to authorized users.