Transcriptome analysis of entorhinal cortex tissue from neuron-specific Sec61a1-overexpressing transgenic mice after AAV-mediated knockdown of Sec61a1 or Adarb2

Expression profiling by high throughput sequencingSEC61A1 is essential for protein translocation and ER function, while ADARB2 is an RNA editor that binds to dsRNA without degradation capability. Previous studies suggest that SEC61A1 overexpression may lead to mitochondrial dsRNA accumulation. To investigate this, we utilized adeno-associated virus (AAV)-mediated shRNA knockdown of Sec61a1 or Adarb2 in the cortex of neuron-specific SEC61A1-overexpressing transgenic mice. After two months, bulk RNA sequencing was performed on cortical tissue to examine transcriptomic changes. This study aims to explore how SEC61A1 overexpression contributes to mitochondrial dsRNA accumulation and how ADARB2, as a dsRNA-binding protein, may influence related pathways.

基于高通量测序的基因表达谱分析：SEC61A1对于蛋白质易位及内质网（ER）功能至关重要，而ADARB2是一种可结合双链RNA（dsRNA）但不具备降解能力的RNA编辑酶。既往研究表明，SEC61A1过表达可能引发线粒体双链RNA积累。为探究这一现象，我们采用腺相关病毒（AAV）介导的短发夹RNA（shRNA）干扰，在神经元特异性过表达SEC61A1的转基因小鼠皮层中敲低Sec61a1或Adarb2的表达。造模两个月后，我们对皮层组织开展批量RNA测序，以分析转录组学变化。本研究旨在明确SEC61A1过表达如何促成线粒体双链RNA积累，以及作为双链RNA结合蛋白的ADARB2可能对相关信号通路产生何种调控作用。