前庭中枢的代偿对眩晕的治疗康复和病后平衡状态至关重要。我们前期研究发现：BDNF/TrkB通路是前庭代偿的关键枢纽；但BDNF表达的上游调控机制却不明。转录起始RNA（tiRNA）是新发现的内源性小非编码RNA，能影响转录因子YY1与转录起始位点结合，调控基因转录。我们前期实验和生物信息学分析示：BDNF基因启动子区存在YY1结合位点；tiRNA能靶向结合YY1位点。据此我们提出假说：小脑-前庭通路中tiRNA抑制YY1结合到BDNF的启动子区，改变染色质立体构象，激活基因转录，最终促进前庭代偿。本课题拟从分子、细胞、组织及动物水平多层次体系明确tiRNA在前庭代偿中的作用；确定tiRNA对BDNF基因转录的调控；揭示tiRNA通过YY1介导BDNF/TrkB通路促进前庭代偿的精细机制。本研究将从tiRNA新视角深入探讨前庭代偿的中枢可塑性，为眩晕治疗及前庭康提供新的理论基础和策略。

Vertigo is one of the most common functionally-disabling conditions that substantially affects the life and work of people. The incidence of vertigo in the general population has been on the rise year by year. However, etiology of vertigo is unclear and strategies standardization for vertigo therapy is urgent. Studies on plasticity mechanism of central vestibular compensation can provide neurobiological information that helps improve the vertigo treatment and vestibular rehabilitation. Our previous studies preliminarily revealed that the brain-derived neurotrophic factor (BDNF) in MVN and flocculus played a pivotal role in vestibular compensation, and transcriptional factor (YY1) could inhibit the activity of the BDNF promoter. Transcription initiation RNA (tiRNA), a novel group of endogenous small non-coding RNAs, can regulate gene transcription via modulating the binding of YY1 with the loci at the transcription initiation site. On the basis of these findings, we were led to hypothesize that tiRNA might regulate the gene transcription of BDNF by working on the target loci of YY1..This research project, by employing Luciferase reporter gene transcription, chromatin immunoprecipitation, nuclear run-on assay, aims to examine the regulatory effects of YY1 on the expression of BDNF promoter and histone modification, and by using RNA and chromatin immunoprecipitation to observe the interaction between tiRNA and YY1 and its features. By constructing a stable system of tiRNA overexpression and inhibition, we will further study the effect of tiRNA expression on the growth, apoptosis, synapse formation and vestibular compensation, with an attempt to understand how tiRNA promote vestibular compensation by modulating the gene transcription of BDNF via YY1 and to find better strategies for vertigo therapy.