Deep sequencing of small non-coding RNA highlights brain-specific expression patterns and RNA cleavage

With the advance of high-throughput sequencing technology numerous new regulatory small RNAs have been identified, that broaden the variety of processing mechanisms and functions of non-coding RNA. Here we explore small non-coding RNA (sncRNA) expression in central parts of the physiological stress and anxiety response system. Therefore, we characterize the sncRNA profile of tissue samples from Amygdala, Hippocampus, Hypothalamus and Adrenal Gland, obtained from 20 pigs. Our analysis reveals that all tissues but Amygdala and Hippocampus possess distinct, tissue-specific expression pattern of miRNA that are associated with Hypoxia, stress responses as well as memory and fear conditioning. In particular, we observe marked differences in the expression profile of limbic tissues compared to those associated to the HPA/stress axis, with a surprisingly high aggregation of 3´-tRNA halves in Amygdala and Hippocampus. Since regulation of sncRNA and RNA cleavage plays a pivotal role in the central nervous system, our work provides seminal insights in the role/involvement of sncRNA in the transcriptional and post-transcriptional regulation of negative emotion, stress and coping behaviour in pigs, and mammals in general.

随着高通量测序技术 (high-throughput sequencing technology) 的进步，大量新型调控型小RNA被成功鉴定，这一进展拓宽了非编码RNA (non-coding RNA) 的加工机制与功能范畴。本研究聚焦生理应激与焦虑应答系统的核心组织，分析小非编码RNA (small non-coding RNA, sncRNA) 的表达模式。为此，我们对20头猪的杏仁核 (Amygdala)、海马体 (Hippocampus)、下丘脑 (Hypothalamus) 与肾上腺 (Adrenal Gland) 组织样本的小非编码RNA表达谱进行了系统表征。分析结果显示，除杏仁核与海马体外，其余三类组织均具备独特的组织特异性微小RNA (microRNA, miRNA) 表达模式，这些微小RNA与缺氧应激、应激应答以及记忆与恐惧条件反射密切相关。尤为关键的是，相较于与HPA/应激轴相关的组织，边缘系统组织的表达谱存在显著差异，其中杏仁核与海马体中3'-tRNA片段 (3´-tRNA halves) 的富集程度远超预期。鉴于小非编码RNA调控与RNA剪切在中枢神经系统中发挥核心作用，本研究揭示了小非编码RNA在猪乃至一般哺乳动物的负面情绪、应激与应对行为的转录及转录后调控中的作用与参与机制，为相关领域提供了开创性的研究见解。