G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum.
G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum.
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G-四链体RNA基序影响恶性疟原虫基因表达
DOI：
10.1093/nar/gkab1095
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发表时间：
2021-12-02
影响因子：
14.9
通讯作者：
Kwok CK
中科院分区：
文献类型：
--
作者：
Dumetz F;Chow EY;Harris LM;Liew SW;Jensen A;Umar MI;Chung B;Chan TF;Merrick CJ;Kwok CK
G-四链体是非螺旋的二级结构，可以在体内在DNA和RNA中折叠。在人类细胞中，它们可以影响DNA中的复制、转录和端粒维持，或RNA的翻译、转录物加工和稳定性。我们以前已经表明，G-四链体是可检测到的疟疾寄生虫恶性疟原虫的DNA，尽管一个非常高的A/T偏置的基因组与异常少的富含鸟嘌呤的序列。在这里，我们使用rG 4-seq进行转录组范围内的结构特异性RNA探测，表明RNA G-四链体也可以在恶性疟原虫RNA中形成。这里通过rG 4seeker管道检测到的许多基序具有非规范形式，并且无法通过标准的计算机算法进行预测。然而，在体外生物物理测定验证非典型图案的形成。恶性疟原虫转录组中的G-四链体经常聚集在某些基因中，并与编码低复杂性肽重复序列的区域相关。它们在特定类别的基因中过度表达，特别是那些编码PfEMP 1毒力因子、应激反应基因和DNA结合蛋白的基因。体外翻译实验和体内翻译效率的测量表明，G-四链体可以影响恶性疟原虫mRNA的翻译。因此，G-四链体是一个新的球员在转录后调控基因表达在这个主要的人类病原体。
G-quadruplexes are non-helical secondary structures that can fold in vivo in both DNA and RNA. In human cells, they can influence replication, transcription and telomere maintenance in DNA, or translation, transcript processing and stability of RNA. We have previously showed that G-quadruplexes are detectable in the DNA of the malaria parasite Plasmodium falciparum, despite a very highly A/T-biased genome with unusually few guanine-rich sequences. Here, we show that RNA G-quadruplexes can also form in P. falciparum RNA, using rG4-seq for transcriptome-wide structure-specific RNA probing. Many of the motifs, detected here via the rG4seeker pipeline, have non-canonical forms and would not be predicted by standard in silico algorithms. However, in vitro biophysical assays verified formation of non-canonical motifs. The G-quadruplexes in the P. falciparum transcriptome are frequently clustered in certain genes and associated with regions encoding low-complexity peptide repeats. They are overrepresented in particular classes of genes, notably those that encode PfEMP1 virulence factors, stress response genes and DNA binding proteins. In vitro translation experiments and in vivo measures of translation efficiency showed that G-quadruplexes can influence the translation of P. falciparum mRNAs. Thus, the G-quadruplex is a novel player in post-transcriptional regulation of gene expression in this major human pathogen.
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