Comparative Transcriptomics Analyses across Species, Organs, and Developmental Stages Reveal Functionally Constrained lncRNAs
Comparative Transcriptomics Analyses across Species, Organs, and Developmental Stages Reveal Functionally Constrained lncRNAs
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DOI：
10.1093/molbev/msz212
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发表时间：
2020-01-01
影响因子：
10.7
通讯作者：
Necsulea, Anamaria
中科院分区：
文献类型：
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作者：
Darbellay, Fabrice;Necsulea, Anamaria
长链非编码RNA（lncRNA）的功能性一直存在争议。一般来说，lncRNA在弱选择压力下，表明大多数lncRNA可能是无功能的。然而，尽管一些调查显示lncRNA扰动的表型效应可以忽略不计，但单个lncRNA的关键生物学作用得到了证实。大多数已证实功能的lncRNA参与基因表达调控，与细胞多能性，分化和器官形态发生相关的途径，表明功能性lncRNA可能在胚胎发育中更丰富，而不是在成年器官中。为了验证这一假设，我们进行了多维比较转录组学分析，跨越五个发育时间点（两个胚胎阶段，新生儿，成年人和老年人），四个器官（脑，肾，肝和睾丸），和三个物种（小鼠，大鼠和鸡）。我们发现，压倒性的，lncRNA优先在成年和老年睾丸中表达，与精子发生过程中允许转录的存在一致。LncRNA通常在发育阶段之间差异表达，并且与成年个体相比，在胚胎和新生儿中的丰度较低，这与发育早期对更严格的表达控制和对噪声转录的更低耐受性的要求一致。对于差异表达的lncRNA，我们发现，在发育阶段之间的表达变化的模式通常是保守的小鼠和大鼠之间。此外，lncRNA在体细胞器官和发育过程中表达高于噪音水平，表现出更高的进化保守性，特别是在其启动子区域。因此，我们表明，功能受限的lncRNA位点在发育器官中富集，我们认为这些位点中的许多可能以RNA独立的方式发挥作用。
The functionality of long noncoding RNAs (lncRNAs) is disputed. In general, lncRNAs are under weak selective pressures, suggesting that the majority of lncRNAs may be nonfunctional. However, although some surveys showed negligible phenotypic effects upon lncRNA perturbation, key biological roles were demonstrated for individual lncRNAs. Most lncRNAs with proven functions were implicated in gene expression regulation, in pathways related to cellular pluripotency, differentiation, and organ morphogenesis, suggesting that functional lncRNAs may be more abundant in embryonic development, rather than in adult organs. To test this hypothesis, we perform a multidimensional comparative transcriptomics analysis, across five developmental time points (two embryonic stages, newborn, adult, and aged individuals), four organs (brain, kidney, liver, and testes), and three species (mouse, rat, and chicken). We find that, overwhelmingly, lncRNAs are preferentially expressed in adult and aged testes, consistent with the presence of permissive transcription during spermatogenesis. LncRNAs are often differentially expressed among developmental stages and are less abundant in embryos and newborns compared with adult individuals, in agreement with a requirement for tighter expression control and less tolerance for noisy transcription early in development. For differentially expressed lncRNAs, we find that the patterns of expression variation among developmental stages are generally conserved between mouse and rat. Moreover, lncRNAs expressed above noise levels in somatic organs and during development show higher evolutionary conservation, in particular, at their promoter regions. Thus, we show that functionally constrained lncRNA loci are enriched in developing organs, and we suggest that many of these loci may function in an RNA-independent manner.