Robic Annie, Cerutti Chloé, Kühn Christa, Faraut Thomas
INRAE, ENVT, GenPhySE, Université de Toulouse, Castanet-Tolosan, France.
Institute Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
Front Genet. 2021 May 10;12:665153. doi: 10.3389/fgene.2021.665153. eCollection 2021.
Circular RNAs have been observed in a large number of species and tissues and are now recognized as a clear component of the transcriptome. Our study takes advantage of functional datasets produced within the FAANG consortium to investigate the pervasiveness of circular RNA transcription in farm animals. We describe here the circular transcriptional landscape in pig, sheep and bovine testicular, muscular and liver tissues using total 66 RNA-seq datasets. After an exhaustive detection of circular RNAs, we propose an annotation of exonic, intronic and sub-exonic circRNAs and comparative analyses of circRNA content to evaluate the variability between individuals, tissues and species. Despite technical bias due to the various origins of the datasets, we were able to characterize some features (i) (ruminant) liver contains more exonic circRNAs than muscle (ii) in testis, the number of exonic circRNAs seems associated with the sexual maturity of the animal. (iii) a particular class of circRNAs, sub-exonic circRNAs, are produced by a large variety of multi-exonic genes (protein-coding genes, long non-coding RNAs and pseudogenes) and mono-exonic genes (protein-coding genes from mitochondrial genome and small non-coding genes). Moreover, for multi-exonic genes there seems to be a relationship between the sub-exonic circRNAs transcription level and the linear transcription level. Finally, sub-exonic circRNAs produced by mono-exonic genes (mitochondrial protein-coding genes, ribozyme, and sno) exhibit a particular behavior. Caution has to be taken regarding the interpretation of the unannotated circRNA proportion in a given tissue/species: clusters of circRNAs without annotation were characterized in genomic regions with annotation and/or assembly problems of the respective animal genomes. This study highlights the importance of improving genome annotation to better consider candidate circRNAs and to better understand the circular transcriptome. Furthermore, it emphasizes the need for considering the relative "weight" of circRNAs/parent genes for comparative analyses of several circular transcriptomes. Although there are points of agreement in the circular transcriptome of the same tissue in two species, it will be not possible to do without the characterization of it in both species.
环状RNA已在大量物种和组织中被观察到，现在被认为是转录组的一个明确组成部分。我们的研究利用FAANG联盟产生的功能数据集来研究家畜中环状RNA转录的普遍性。我们在此使用总共66个RNA测序数据集描述猪、绵羊和牛的睾丸、肌肉和肝脏组织中的环状转录图谱。在对环状RNA进行详尽检测后，我们提出了外显子、内含子和亚外显子环状RNA的注释，并对环状RNA含量进行比较分析，以评估个体、组织和物种之间的变异性。尽管由于数据集的各种来源存在技术偏差，但我们能够表征一些特征：（i）（反刍动物）肝脏中的外显子环状RNA比肌肉中的多；（ii）在睾丸中，外显子环状RNA的数量似乎与动物的性成熟有关；（iii）一类特殊的环状RNA，即亚外显子环状RNA，由多种多外显子基因（蛋白质编码基因、长链非编码RNA和假基因）和单外显子基因（线粒体基因组的蛋白质编码基因和小非编码基因）产生。此外，对于多外显子基因，亚外显子环状RNA转录水平与线性转录水平之间似乎存在关系。最后，由单外显子基因（线粒体蛋白质编码基因、核酶和小核仁RNA）产生的亚外显子环状RNA表现出特殊行为。对于给定组织/物种中未注释的环状RNA比例的解释必须谨慎：在相应动物基因组存在注释和/或组装问题的基因组区域中，鉴定出了没有注释的环状RNA簇。这项研究强调了改进基因组注释以更好地考虑候选环状RNA并更好地理解环状转录组的重要性。此外，它强调了在比较多个环状转录组时考虑环状RNA/亲本基因的相对“权重”的必要性。尽管两个物种相同组织的环状转录组存在一些一致点，但如果不在两个物种中对其进行表征，就不可能做到全面了解。
