Discovery of long non-coding RNAs in the liver fluke, Fasciola hepatica.
Discovery of long non-coding RNAs in the liver fluke, Fasciola hepatica.
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DOI：
10.1371/journal.pntd.0011663
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发表时间：
2023-09
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
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长链非编码（lnc）RNA是一类真核RNA，其不编码蛋白质，并且与转录调控以及无数其他功能相关联。使用自定义的计算机流水线，我们已经在肝吸虫寄生虫肝片吸虫中鉴定了6，436个推定的lncRNA转录本，其中没有一个与先前描述的曼氏血吸虫的转录本保守。F. Hepatica lncRNA与F.肝组织mRNA的转录长度、编码概率、外显子/内含子组成、表达模式和基因组分布。RNA-Seq和数字液滴PCR测量结果表明，在哺乳动物内的生命阶段之间，lncRNA的表达受到发育调控; lncRNA（14.2%）和mRNA（12.8%）的差异表达比例相似（p<0.001），支持lncRNA在F.肝的生命阶段。虽然大多数lncRNA（81%）是基因间的，我们确定了一些重叠的蛋白质编码位点的反义（13%）或内含子（6%）的配置。我们没有发现明确的证据，相关的发育表达内的位置相关的lncRNA：mRNA对，但全球共表达分析确定了5 lncRNA，反向共调节89 mRNA，包括大量的功能必需的蛋白酶。在3135个lncRNA中存在微（mi）RNA结合位点表明lncRNA的基于miRNA的转录后调节的潜力，和/或它们作为竞争性内源（ce）RNA的功能。相同的注释管道在F.南极洲这是在F. Hepatica为未来的功能和比较基因组学研究提供了一条途径，这将为寄生虫生物学的一个知之甚少的方面提供一个新的视角。随着对基因组和转录组的理解的增加，与分子生物学的中心法则相反，并非所有的RNA都编码蛋白质已经变得很清楚。然而，许多这样的“非编码”RNA有自己的功能。例如，长非编码（lnc）RNA包含大比例的人类基因组并且控制一些人类蛋白质编码基因的表达。在寄生虫中，lncRNA仍然研究不足，知之甚少。本文首次描述了肝片吸虫lncRNA补体。我们发现，lncRNA表达的变化，寄生虫的发展，以类似的方式蛋白质编码的mRNA，这表明寄生虫的生长和发育中的重要作用。一些lncRNA显示出与编码重要寄生虫蛋白的mRNA相关的发育表达，表明它们可能相互作用，表明吸虫lncRNA的调节功能。lncRNA的较大子集可以与微（mi）RNA相互作用，微（mi）RNA是另一种类型的非编码RNA，是真核生物中基因表达的重要调节因子。这些相互作用再次为我们理解吸虫lncRNA生物学提供了重要补充。我们的最终目标是找到抑制这些相互作用的方法，这些方法可以用于治疗吸虫感染的新药，这是农业的全球性灾难。
Long non-coding (lnc)RNAs are a class of eukaryotic RNA that do not code for protein and are linked with transcriptional regulation, amongst a myriad of other functions. Using a custom in silico pipeline we have identified 6,436 putative lncRNA transcripts in the liver fluke parasite, Fasciola hepatica, none of which are conserved with those previously described from Schistosoma mansoni. F. hepatica lncRNAs were distinct from F. hepatica mRNAs in transcript length, coding probability, exon/intron composition, expression patterns, and genome distribution. RNA-Seq and digital droplet PCR measurements demonstrated developmentally regulated expression of lncRNAs between intra-mammalian life stages; a similar proportion of lncRNAs (14.2%) and mRNAs (12.8%) were differentially expressed (p<0.001), supporting a functional role for lncRNAs in F. hepatica life stages. While most lncRNAs (81%) were intergenic, we identified some that overlapped protein coding loci in antisense (13%) or intronic (6%) configurations. We found no unequivocal evidence for correlated developmental expression within positionally correlated lncRNA:mRNA pairs, but global co-expression analysis identified five lncRNA that were inversely co-regulated with 89 mRNAs, including a large number of functionally essential proteases. The presence of micro (mi)RNA binding sites in 3135 lncRNAs indicates the potential for miRNA-based post-transcriptional regulation of lncRNA, and/or their function as competing endogenous (ce)RNAs. The same annotation pipeline identified 24,141 putative lncRNAs in F. gigantica. This first description of lncRNAs in F. hepatica provides an avenue to future functional and comparative genomics studies that will provide a new perspective on a poorly understood aspect of parasite biology. With increased understanding of genomes and transcriptomes it has become clear that not all RNAs code for protein, in contrast to the Central Dogma of molecular biology. Nevertheless, many such “non-coding” RNAs have functions in their own right. For example, long non-coding (lnc)RNAs comprise a large proportion of the human genome and control expression of some human protein coding genes. In parasites, lncRNAs remain understudied and poorly understood. This paper provides the first description of the lncRNA complement of the liver fluke, Fasciola hepatica. We show that lncRNA expression changes as parasites develop, in a similar manner to protein-coding mRNA, suggesting important roles in parasite growth and development. Some lncRNAs show correlated developmental expression with mRNAs coding for important parasite proteins, suggesting that they may interact, suggesting regulatory functions for fluke lncRNAs. A larger subset of lncRNA may interact with micro (mi)RNAs, another type of non-coding RNA that are important regulators of gene expression in eukaryotes. These interactions are, again, important additions to our understanding of fluke lncRNA biology. Our ultimate goal is to discover ways to inhibit these interactions that could be used for new medicines for fluke infections which are a global scourge on the farming industry.
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影响因子：
14.9
作者：
Kim DS;Cho CY;Huh JW;Kim HS;Cho HG
通讯作者：
Cho HG
影响因子：
3.8
作者：
Etebari K;Asad S;Zhang G;Asgari S
通讯作者：
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影响因子：
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作者：
Clemson, CM;McNeil, JA;Willard, HF;Lawrence, JB
通讯作者：
Lawrence, JB
DOI：
10.1074/mcp.ra117.000445
发表时间：
2018-04
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
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通讯作者：
Dalton JP
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影响因子：
1.5
作者：
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通讯作者：
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