解耦转录组层:环状rna的独特和可变性质。

IF 4.5 1区 生物学 Q1 BIOLOGY
María Alonso-García, Laurence Liaubet, Thomas Faraut, Patrice Dehais, Christa Kühn, Julie Demars, Beatriz Gutiérrez-Gil, Annie Robic
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引用次数: 0

摘要

背景:环状rna (circRNAs)和mrna是来自同一基因的不同转录本,通过不同的剪接机制产生。本研究探讨了环形转录组相对于线性转录组在生物条件和组织中的行为。我们分析了36个牛单核细胞源性巨噬细胞(MDM)样本的转录组学数据,这些样本是在离体鸟分枝杆菌ssp中收集的。副结核(MAP)感染实验,按约翰氏病(JD)抗体状态(JD+或JD-)和感染情况(对照组或MAP感染)分层。我们将分析扩展到健康的牛组织,包括新生儿和青春期后的睾丸,以及按性别和饲料效率分层的12只动物的肝脏和肌肉样本。结果:在36个MDM样本中,我们鉴定出来自1895个基因的3358个外显子环状rna。通过比较环状rna和线性转录本的平均表达水平,并考虑到表达基因的数量,我们估计环状转录组大约比线性转录组小100倍。对圆形和线性转录组的分析表明,MAP感染仅影响MDM_JD-的线性转录组。其他三个转录组-环状JD-,环状JD+和线性JD+ -没有表现出感染特异性反应。在睾丸中,成熟与圆形和线性转录组的深刻但不协调的变化有关。当环状rna丰度下降时,线性转录组经历了以新基因激活为标志的完全重组。在肝脏中,雌性样本仅在考虑整个线性转录组和顶部表达的环状转录组时才按饲料效率进行聚类。在MDMs中,对照和感染样本的环状转录组以及JD+线性转录组以供体特异性特征为主。相反,JD-线性转录组反映了MAP感染,感染特异性结构高于个体间差异。结论:在MDM和组织样本中,环状和线性转录组遵循截然不同且在很大程度上独立的调控逻辑。虽然两者都捕获了个体间的差异,但circRNA的表达似乎更具可变性,并且可能携带较少的生理信号,特别是当在相应的线性转录组中没有检测到明确的表型特征时。这些发现表明,环状和线性rna来自互补和非冗余的基因调控层,强调了并行分析两者的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Decoupling transcriptome layers: the distinct and variable nature of circular RNAs.

Background: Circular RNAs (circRNAs) and mRNAs are distinct transcripts from the same genes, produced by different splicing mechanisms. This study investigates the behavior of the circular transcriptome relative to the linear one across biological conditions and tissues. We analyzed transcriptomic data from 36 bovine monocyte-derived macrophage (MDM) samples collected during an ex vivo Mycobacterium avium ssp. paratuberculosis (MAP) infection experiment, stratified by Johne's disease (JD) antibody status (JD+ or JD-) and by infection condition (control or MAP infected). We extended our analysis to healthy bovine tissues, including neonatal and post-pubertal testes, and liver and muscle samples from 12 animals stratified by sex and feed efficiency.

Results: In the 36 MDM samples, we identified 3358 exonic circRNAs derived from 1895 genes. By comparing the mean expression levels of circRNAs and linear transcripts, and considering the number of expressed genes, we estimate that the circular transcriptome is approximately 100 times smaller than the linear transcriptome. Analyses of the circular and linear transcriptomes revealed that MAP infection impacted only the linear transcriptome of MDM_JD- . The other three transcriptomes-circular JD- , circular JD+ , and linear JD+ -showed no infection-specific response. In the testes, maturation was associated with profound but uncoordinated changes in the circular and linear transcriptomes. While circRNA abundance declined, the linear transcriptome underwent a complete reorganization marked by the activation of novel genes. In the liver, female samples clustered by feed efficiency only when the entire linear and top-expressed circular transcriptomes were considered, respectively. In MDMs, the circular transcriptomes of control and infected samples, as well as the JD+ linear transcriptome, were dominated by donor-specific signatures. In contrast, the JD- linear transcriptome reflected MAP infection, with infection-specific structuring overriding inter-individual variation.

Conclusions: In both MDM and tissue samples, circular and linear transcriptomes follow distinct and largely independent regulatory logics. While both capture inter-individual variation, circRNA expression appears more variable and may carry fewer physiological signals, especially when no clear phenotypic signature has been detected in the corresponding linear transcriptome. These findings demonstrate that circular and linear RNAs arise from complementary and nonredundant layers of gene regulation, emphasizing the importance of analyzing both in parallel.

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来源期刊
BMC Biology
BMC Biology 生物-生物学
CiteScore
7.80
自引率
1.90%
发文量
260
审稿时长
3 months
期刊介绍: BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.
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