Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni.
Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni.
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曼氏血吸虫长链非编码RNA水平可被5-氮胞苷调节
DOI：
10.1038/s41598-020-78669-5
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发表时间：
2020-12-09
影响因子：
4.6
通讯作者：
Verjovski-Almeida S
中科院分区：
文献类型：
--
作者：
Amaral MS;Maciel LF;Silveira GO;Olberg GGO;Leite JVP;Imamura LK;Pereira ASA;Miyasato PA;Nakano E;Verjovski-Almeida S
曼氏血吸虫是一种引起血吸虫病的扁形虫，这是一种被忽视的热带疾病，影响着全球2亿多人。只有一种药物适用于治疗，吡喹酮，这可能导致寄生虫抗药性的出现。核糖核苷类似物5-氮杂胞苷（5-AzaC）是一种抑制S.通过干扰寄生虫的转录、翻译和干细胞活动来影响曼氏曼氏菌产卵和卵巢发育。因此，研究5-AzaC对S. mansoni可能有助于发现新的药物靶点。长链非编码RNA（longnoncodingRNA，lncRNA）是一类长度超过200个核苷酸的转录本，具有低或无蛋白质编码潜力，参与生殖、干细胞维持和耐药性等生物学过程。我们最近发表了一个在S. mansoni生命周期阶段、组织和单细胞。然而，它仍然在很大程度上是未知的，如果lncRNA响应寄生虫的表观遗传药物。在这里，我们通过RNA-Seq重新分析表明，在体外5-AzaC处理S. mansoni雌性，包括基因间、反义和正义lncRNA。这些lncRNA中的许多属于与男性代谢相关的共表达网络模块，并且与配对的女性和卵巢相比，在未配对中也差异表达。这些lncRNA中有一半在其基因组位点具有组蛋白标记，表明通过组蛋白修饰进行调节。在选定的一组8个lncRNA中，通过RT-qPCR验证了其中一半在女性中差异表达，并且其中一些也在男性中差异表达。有趣的是，这些lncRNA也在其他生命周期阶段表达。这项研究表明，许多lncRNA可能参与了S。mansoni的生殖生物学是由5-AzaC调节的，并揭示了探索lncRNA在寄生虫中响应药物治疗的相关性。
Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects more than 200 million people worldwide. There is only one drug indicated for treatment, praziquantel, which may lead to parasite resistance emergence. The ribonucleoside analogue 5-azacytidine (5-AzaC) is an epigenetic drug that inhibits S. mansoni oviposition and ovarian development through interference with parasite transcription, translation and stem cell activities. Therefore, studying the downstream pathways affected by 5-AzaC in S. mansoni may contribute to the discovery of new drug targets. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein coding potential that have been involved in reproduction, stem cell maintenance and drug resistance. We have recently published a catalog of lncRNAs expressed in S. mansoni life-cycle stages, tissues and single cells. However, it remains largely unknown if lncRNAs are responsive to epigenetic drugs in parasites. Here, we show by RNA-Seq re-analyses that hundreds of lncRNAs are differentially expressed after in vitro 5-AzaC treatment of S. mansoni females, including intergenic, antisense and sense lncRNAs. Many of these lncRNAs belong to co-expression network modules related to male metabolism and are also differentially expressed in unpaired compared with paired females and ovaries. Half of these lncRNAs possess histone marks at their genomic loci, indicating regulation by histone modification. Among a selected set of 8 lncRNAs, half of them were validated by RT-qPCR as differentially expressed in females, and some of them also in males. Interestingly, these lncRNAs are also expressed in other life-cycle stages. This study demonstrates that many lncRNAs potentially involved with S. mansoni reproductive biology are modulated by 5-AzaC and sheds light on the relevance of exploring lncRNAs in response to drug treatments in parasites.
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DOI：
10.1038/nrm4043
发表时间：
2015-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Du J;Johnson LM;Jacobsen SE;Patel DJ
通讯作者：
Patel DJ
影响因子：
9.6
作者：
Cosseau C;Wolkenhauer O;Padalino G;Geyer KK;Hoffmann KF;Grunau C
通讯作者：
Grunau C
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
DOI：
10.1016/j.ijpddr.2014.03.001
发表时间：
2014-08
影响因子：
4
作者：
Britton, Collette;Winter, Alan D.;Gillan, Victoria;Devaney, Eileen
通讯作者：
Devaney, Eileen
ncDR：与耐药性相关的非编码 RNA 的综合资源。
影响因子：
5.8
作者：
Dai, Enyu;Yang, Feng;Jiang, Wei
通讯作者：
Jiang, Wei