Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland, USA.
RNA Biol. 2021 Aug;18(8):1160-1169. doi: 10.1080/15476286.2020.1836456. Epub 2020 Nov 1.
The auditory system is a complex sensory network with an orchestrated multilayer regulatory programme governing its development and maintenance. Accumulating evidence has implicated long non-coding RNAs (lncRNAs) as important regulators in numerous systems, as well as in pathological pathways. However, their function in the auditory system has yet to be explored. Using a set of specific criteria, we selected four lncRNAs expressed in the mouse cochlea, which are conserved in the human transcriptome and are relevant for inner ear function. Bioinformatic characterization demonstrated a lack of coding potential and an absence of evolutionary conservation that represent properties commonly shared by their class members. RNAscope® analysis of the spatial and temporal expression profiles revealed specific localization to inner ear cells. Sub-cellular localization analysis presented a distinct pattern for each lncRNA and mouse tissue expression evaluation displayed a large variability in terms of level and location. Our findings establish the expression of specific lncRNAs in different cell types of the auditory system and present a potential pathway by which the lncRNA acts in the inner ear. Studying lncRNAs and deciphering their functions may deepen our knowledge of inner ear physiology and morphology and may reveal the basis of as yet unresolved genetic hearing loss-related pathologies. Moreover, our experimental design may be employed as a reference for studying other inner ear-related lncRNAs, as well as lncRNAs expressed in other sensory systems.
听觉系统是一个复杂的感觉网络,其发育和维持受到多层次调控程序的协调控制。越来越多的证据表明,长非编码 RNA(lncRNA)作为许多系统以及病理途径中的重要调节剂。然而,它们在听觉系统中的功能尚未被探索。我们使用了一组特定的标准,选择了在小鼠耳蜗中表达的四个 lncRNA,这些 lncRNA 在人类转录组中保守,与内耳功能相关。生物信息学特征分析表明它们缺乏编码潜力和进化保守性,这是它们所属类别成员的共同特征。RNAscope®分析时空表达谱显示出特定的内耳细胞定位。每个 lncRNA 的亚细胞定位分析呈现出独特的模式,而小鼠组织表达评估在水平和位置上显示出很大的可变性。我们的研究结果确立了特定 lncRNA 在听觉系统不同细胞类型中的表达,并提出了 lncRNA 在内耳中作用的潜在途径。研究 lncRNA 并阐明其功能可以加深我们对内耳生理学和形态学的认识,并揭示尚未解决的遗传性听力损失相关病理学的基础。此外,我们的实验设计可以作为研究其他内耳相关 lncRNA 以及其他感觉系统表达的 lncRNA 的参考。