School of Life Sciences, Shandong University of Technology, 266 Xincun Western Road, Zibo, 255049, People's Republic of China.
Institute of Organismic and Molecular Evolution (iOME), Anthropology, Anselm-Franz-von-Bentzel-Weg 7, Johannes Gutenberg University, 55099, Mainz, Germany.
BMC Genomics. 2020 Dec 7;21(1):876. doi: 10.1186/s12864-020-07234-1.
Planarians reliably regenerate all body parts after injury, including a fully functional head and central nervous system. But until now, the expression dynamics and functional role of miRNAs and other small RNAs during the process of head regeneration are not well understood. Furthermore, little is known about the evolutionary conservation of the relevant small RNAs pathways, rendering it difficult to assess whether insights from planarians will apply to other taxa.
In this study, we applied high throughput sequencing to identify miRNAs, tRNA fragments and piRNAs that are dynamically expressed during head regeneration in Dugesia japonica. We further show that knockdown of selected small RNAs, including three novel Dugesia-specific miRNAs, during head regeneration induces severe defects including abnormally small-sized eyes, cyclopia and complete absence of eyes.
Our findings suggest that a complex pool of small RNAs takes part in the process of head regeneration in Dugesia japonica and provide novel insights into global small RNA expression profiles and expression changes in response to head amputation. Our study reveals the evolutionary conserved role of miR-124 and brings further promising candidate small RNAs into play that might unveil new avenues for inducing restorative programs in non-regenerative organisms via small RNA mimics based therapies.
涡虫在受伤后能可靠地再生所有身体部位,包括一个功能齐全的头部和中枢神经系统。但直到现在,miRNA 和其他小 RNA 在头部再生过程中的表达动态和功能作用还不是很清楚。此外,关于相关小 RNA 途径的进化保守性知之甚少,这使得很难评估从涡虫中获得的见解是否适用于其他分类群。
在这项研究中,我们应用高通量测序来鉴定在日本三角涡虫头部再生过程中动态表达的 miRNAs、tRNA 片段和 piRNAs。我们进一步表明,在头部再生过程中敲低选定的小 RNA,包括三种新的日本三角涡虫特异性 miRNA,会导致严重的缺陷,包括眼睛异常小、独眼和完全没有眼睛。
我们的研究结果表明,在日本三角涡虫头部再生过程中,存在着复杂的小 RNA 池,并为全球小 RNA 表达谱以及对头部截肢的反应中的表达变化提供了新的见解。我们的研究揭示了 miR-124 在进化上的保守作用,并进一步提出了有希望的候选小 RNA,它们可能通过基于小 RNA 模拟物的治疗为诱导非再生生物的修复程序开辟新的途径。