SAFA-LncRNA调节抗病毒固有免疫基因染色质开放性的功能和机制研究

固有免疫是机体抵抗感染的第一道防线，研究固有免疫调节对认识和治疗感染相关疾病具有重要意义。随着高通量测序技术的发展，全基因组层面高纬度、动态化特征的基因表达调控研究成为世界前沿热点。申请人前期工作发现脚手架蛋白SAFA偶联固有免疫和染色质重塑，在介导抗病毒相关基因表达及增强子/超级增强子激活方面发挥重要的作用。但SAFA介导染色质重塑的具体机制并不清楚。我们预实验结果显示SAFA的功能发挥依赖其RNA结合结构域，且病毒感染诱导长链非编码RNA与SAFA的结合。SAFA缺失导致病毒诱导固有免疫相关染色质的开放性明显减弱。本项目将从全基因组角度研究SAFA如何特异性调控抗病毒免疫基因的染色质开放性，重点探讨长链非编码RNA在其中发挥的功能和分子机制。

Innate immunity defines the first line of host defense against foreign microorganisms. In recent years, the emergence and increasing maturity of high-throughput sequencing technology provide the opportunity for in-depth research in the field. Research on the global regulation of innate immune gene expression has become an area of extensive research. Our previous works find that the nuclear matrix protein SAFA, which connects innate immunity and chromatin remodeling, surveils viral RNA and facilitates innate immune response by activating antiviral enhancers and super-enhancers. However, the specific regulatory mechanism of SAFA in mediating chromatin remodeling is not clear. The RNA binding domain of SAFA is critical for antiviral responses. Our preliminary results showed that viral infection induced long non-coding RNA production and binding to SAFA. SAFA deficiency impaired the chromatin accessibility after viral infection. In the future, we will further study the mechanism of SAFA mediated chromatin remodeling from a genome-wide perspective. Our study will provide better understanding to immunological diseases and therapeutic targets to cure infectious diseases.