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全基因组鉴定和长非编码 RNA 在听觉和前庭系统中的表达谱分析。

Genome-wide identification and expression profiling of long non-coding RNAs in auditory and vestibular systems.

机构信息

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, 6997801, Israel.

Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 7610001, Israel.

出版信息

Sci Rep. 2017 Aug 17;7(1):8637. doi: 10.1038/s41598-017-08320-3.

Abstract

Mammalian genomes encode multiple layers of regulation, including a class of RNA molecules known as long non-coding RNAs (lncRNAs). These are >200 nucleotides in length and similar to mRNAs, they are capped, polyadenylated, and spliced. In contrast to mRNAs, lncRNAs are less abundant and have higher tissue specificity, and have been linked to development, epigenetic processes, and disease. However, little is known about lncRNA function in the auditory and vestibular systems, or how they play a role in deafness and vestibular dysfunction. To help address this need, we performed a whole-genome identification of lncRNAs using RNA-seq at two developmental stages of the mouse inner ear sensory epithelium of the cochlea and vestibule. We identified 3,239 lncRNA genes, most of which were intergenic (lincRNAs) and 721 are novel. We examined temporal and tissue specificity by analyzing the developmental profiles on embryonic day 16.5 and at birth. The spatial and temporal patterns of three lncRNAs, two of which are in proximity to genes associated with hearing and deafness, were explored further. Our findings indicate that lncRNAs are prevalent in the sensory epithelium of the mouse inner ear and are likely to play key roles in regulating critical pathways for hearing and balance.

摘要

哺乳动物基因组编码多层次的调控,包括一类被称为长非编码 RNA(lncRNA)的 RNA 分子。这些 RNA 的长度超过 200 个核苷酸,与 mRNA 相似,它们具有帽结构、多聚腺苷酸化和剪接。与 mRNA 不同,lncRNA 丰度较低,组织特异性较高,与发育、表观遗传过程和疾病有关。然而,关于 lncRNA 在听觉和前庭系统中的功能,以及它们在耳聋和前庭功能障碍中的作用,知之甚少。为了满足这一需求,我们使用 RNA-seq 在小鼠内耳耳蜗和前庭感觉上皮的两个发育阶段进行了全基因组 lncRNA 的鉴定。我们鉴定了 3239 个 lncRNA 基因,其中大多数是基因间(lincRNAs),721 个是新的。我们通过分析胚胎 16.5 天和出生时的发育图谱来研究它们的时间和组织特异性。进一步探索了三个 lncRNA 的时空表达模式,其中两个位于与听力和耳聋相关基因附近。我们的研究结果表明,lncRNA 在小鼠内耳感觉上皮中普遍存在,可能在调控听力和平衡的关键途径中发挥关键作用。

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