Revealing stage-specific expression patterns of long noncoding RNAs along mouse spermatogenesis

Revealing stage-specific expression patterns of long noncoding RNAs along mouse spermatogenesis
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DOI:
10.1080/15476286.2019.1700332
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发表时间:
2019-12-25
期刊:
影响因子:
4.1
通讯作者:
Geisinger, Adriana
Geisinger, Adriana
中科院分区:
生物学3区
文献类型:
--
作者:
Trovero, Maria F.;Rodriguez-Casuriaga, Rosana;Geisinger, Adriana

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大量长链非编码RNA(lncRNA)的发现,以及它们在不同生物过程中发挥关键作用的发现,为理解基因调控提供了新的视角。已经显示,在不同脊椎动物组织中,睾丸表达最高量的lncRNA。然而,尽管一些研究已经解决了lncRNA沿着精子发生的特征,lncRNA在其不同阶段的差异表达的详尽分析仍然缺乏。在这里,我们提出的结果lncRNA转录谱沿着小鼠精子发生,采用高纯度的流式分选的生精阶段特异性细胞群,链特异性RNAseq,并结合最新的生物信息学管道进行分析。我们发现绝大多数睾丸lncRNA基因在减数分裂后阶段(即精子发生)表达,其特征在于广泛的转录后调控。不同生精阶段的LncRNA在转录长度、外显子数目和生物型方面具有共同的特征。大部分lncRNA是lincRNA,其次是反义(AS)lncRNA。共表达分析显示AS lncRNA及其重叠蛋白编码基因的表达模式在不同的生精阶段转换之间具有高度的沿着相关性,这为lncRNA相关的调控机制提供了可能的线索。有趣的是,我们观察到的AS lncRNA和其主机的正义mRNA的共定位在拟染色体体,一个圆形的精子细胞特异性的细胞器,已被提出作为一个水库的RNA相关的监管机制。另一个有趣的观察结果是Y连锁睾丸lncRNA几乎完全缺乏可检测的表达,尽管该染色体注释了大量lncRNA基因。
The discovery of a large number of long noncoding RNAs (lncRNAs), and the finding that they may play key roles in different biological processes, have started to provide a new perspective in the understanding of gene regulation. It has been shown that the testes express the highest amount of lncRNAs among different vertebrate tissues. However, although some studies have addressed the characterization of lncRNAs along spermatogenesis, an exhaustive analysis of the differential expression of lncRNAs at its different stages is still lacking. Here, we present the results for lncRNA transcriptome profiling along mouse spermatogenesis, employing highly pure flow sorted spermatogenic stage-specific cell populations, strand-specific RNAseq, and a combination of up-to-date bioinformatic pipelines for analysis. We found that the vast majority of testicular lncRNA genes are expressed at post-meiotic stages (i.e. spermiogenesis), which are characterized by extensive post-transcriptional regulation. LncRNAs at different spermatogenic stages shared common traits in terms of transcript length, exon number, and biotypes. Most lncRNAs were lincRNAs, followed by a high representation of antisense (AS) lncRNAs. Co-expression analyses showed a high correlation along the different spermatogenic stage transitions between the expression patterns of AS lncRNAs and their overlapping protein-coding genes, raising possible clues about lncRNA-related regulatory mechanisms. Interestingly, we observed the co-localization of an AS lncRNA and its host sense mRNA in the chromatoid body, a round spermatids-specific organelle that has been proposed as a reservoir of RNA-related regulatory machinery. An additional, intriguing observation is the almost complete lack of detectable expression for Y-linked testicular lncRNAs, despite that a high number of lncRNA genes are annotated for this chromosome.