Innate Immunity & RNA Science

Decoding How Cells Distinguish Self from Non-SeIf RNA！

Dr. Hu has been dedicated to studying the mechanisms of nucleic acid immunity, with a focus on the regulation of endogenous double-stranded RNA (dsRNA). His research has uncovered multiple regulatory pathways of endogenous dsRNA and revealed the immune tolerance mechanisms that prevent self-dsRNA from triggering autoimmune responses. His key research contributions include:

1. Discover mechanisms by which cells avoid innate immune responses to self-dsRNA: Dr. Hu demonstrated that the RNA-editing enzyme ADAR1 suppresses the activation of dsRNA immune receptors MDA5 and PKR through two distinct molecular mechanisms. ADAR1 edits endogenous dsRNA to prevent its recognition by MDA5 and competitively binds to dsRNA to inhibit PKR activation (Hu et al., Molecular Cell, 2023). This study provided significant insights into how cells prevent immune responses to self-dsRNA, offering a theoretical basis for understanding autoimmune diseases and developing tumor immunotherapies.

2. Uncover the regulatory mechanism and function of dsRNA nuclear retention mediated by paraspeckles: Dr. Hu’s research showed that endogenous dsRNA is retained in the nucleus by paraspeckles, a type of nuclear bodies, and that this retention is regulated by stimuli and mitochondrial stress (Hu et al., Genes and Development, 2015; Wang, Hu et al., Nature Cell Biology, 2018). These findings expanded the understanding of gene expression regulation by systematically elucidating the nuclear retention mechanism of dsRNA, providing a foundation for further investigation into the regulation and function of endogenous dsRNA.

3. Invent vector for expressing nucleic acid in the nucleus: Dr. Hu contributed to the development of a novel vector that enables nucleic acids to be expressed and enriched in the nucleus (Yin, Hu et al., Nucleic Acids Research, 2015). This tool has become a valuable resource for studying the functions of nuclear long non-coding RNAs (lncRNAs).