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多核糖体谱分析揭示了人类疟原虫恶性疟原虫中基因表达的翻译控制。

Polysome profiling reveals translational control of gene expression in the human malaria parasite Plasmodium falciparum.

作者信息

Bunnik Evelien M, Chung Duk-Won Doug, Hamilton Michael, Ponts Nadia, Saraf Anita, Prudhomme Jacques, Florens Laurence, Le Roch Karine G

出版信息

Genome Biol. 2013 Nov 22;14(11):R128. doi: 10.1186/gb-2013-14-11-r128.

Abstract

BACKGROUND

In eukaryotic organisms, gene expression is regulated at multiple levels during the processes of transcription and translation. The absence of a tight regulatory network for transcription in the human malaria parasite suggests that gene expression may largely be controlled at post-transcriptional and translational levels.

RESULTS

In this study, we compare steady-state mRNA and polysome-associated mRNA levels of Plasmodium falciparum at different time points during its asexual cell cycle. For more than 30% of its genes, we observe a delay in peak transcript abundance in the polysomal fraction as compared to the steady-state mRNA fraction, suggestive of strong translational control. Our data show that key regulatory mechanisms could include inhibitory activity of upstream open reading frames and translational repression of the major virulence gene family by intronic transcripts. In addition, we observe polysomal mRNA-specific alternative splicing events and widespread transcription of non-coding transcripts.

CONCLUSIONS

These different layers of translational regulation are likely to contribute to a complex network that controls gene expression in this eukaryotic pathogen. Disrupting the mechanisms involved in such translational control could provide novel anti-malarial strategies.

摘要

背景

在真核生物中,基因表达在转录和翻译过程中受到多个层面的调控。人类疟原虫缺乏紧密的转录调控网络,这表明基因表达可能在很大程度上受转录后和翻译水平的控制。

结果

在本研究中,我们比较了恶性疟原虫在其无性细胞周期不同时间点的稳态mRNA水平和多核糖体相关mRNA水平。对于超过30%的基因,我们观察到与稳态mRNA部分相比,多核糖体部分的转录本丰度峰值出现延迟,这表明存在强大的翻译控制。我们的数据表明,关键调控机制可能包括上游开放阅读框的抑制活性以及内含子转录本对主要毒力基因家族的翻译抑制。此外,我们观察到多核糖体mRNA特异性可变剪接事件以及非编码转录本的广泛转录。

结论

这些不同层面的翻译调控可能有助于形成一个控制这种真核病原体基因表达的复杂网络。破坏参与这种翻译控制的机制可能提供新的抗疟策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc8d/4053746/e2220ff9d346/gb-2013-14-11-r128-1.jpg

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