Transcriptome-wide dynamics of extensive m(6)A mRNA methylation during Plasmodium falciparum blood-stage development.
Transcriptome-wide dynamics of extensive m(6)A mRNA methylation during Plasmodium falciparum blood-stage development.
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DOI：
10.1038/s41564-019-0521-7
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发表时间：
2019-12
影响因子：
28.3
通讯作者：
Scherf A
中科院分区：
文献类型：
--
作者：
Baumgarten S;Bryant JM;Sinha A;Reyser T;Preiser PR;Dedon PC;Scherf A
疟疾发病机制源于恶性疟原虫在人红细胞内的无性复制，它依赖于48小时生命周期内精确定时的基因级联表达。尽管已经观察到这种硬连线程序的大量转录后调节，但仍不清楚这些过程如何在转录组范围内介导。为此，我们鉴定了恶性疟原虫转录组中的mRNA修饰，并在血液期发育过程中对n6 -甲基腺苷（m6A）进行了全面表征。通过质谱分析和m6A RNA测序，我们证明m6A是高度发育调控的，超过了任何其他真核生物中已知的m6A水平。我们描述了一种独特的m6A写入复合物，并表明通过CRISPR干扰敲低假定的m6A甲基转移酶PfMT-A70会导致通常含有m6A的转录本水平增加。因此，我们发现m6A甲基化与mRNA稳定性或翻译效率呈负相关。我们进一步鉴定了两种可能与m6a结合的YTH蛋白，它们可能参与了寄生虫生命周期中这些过程的调节。我们的数据展示了疟原虫中广泛的m6A mRNA甲基化程序的独特特征，并揭示了其在动态微调单细胞真核生物转录级联中的关键作用。
Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-h life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood-stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We characterize a distinct m6A writer complex and show that knockdown of the putative m6A methyltransferase, PfMT-A70, by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A methylation and mRNA stability or translational efficiency. We further identify two putative m6A-binding YTH proteins that are likely to be involved in the regulation of these processes across the parasite’s life cycle. Our data demonstrate unique features of an extensive m6A mRNA methylation programme in malaria parasites and reveal its crucial role in dynamically fine-tuning the transcriptional cascade of a unicellular eukaryote.
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影响因子：
5.2
作者：
Cui L;Lindner S;Miao J
通讯作者：
Miao J
影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
7.7
作者：
Caro F;Ahyong V;Betegon M;DeRisi JL
通讯作者：
DeRisi JL
影响因子：
6.7
作者：
Ganesan K;Ponmee N;Jiang L;Fowble JW;White J;Kamchonwongpaisan S;Yuthavong Y;Wilairat P;Rathod PK
通讯作者：
Rathod PK