HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex (HDP-RNP) (HDP-RNP)

The HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein (HDP-RNP) complex is a multi-subunit nuclear assembly that acts as a critical regulator of the innate immune response to double-stranded DNA. It is composed of the transcriptional inhibitor HEXIM1, the long non-coding RNA NEAT1, the DNA-dependent protein kinase (DNA-PK) complex (PRKDC, XRCC5/Ku80, and XRCC6/Ku70), and several paraspeckle-associated proteins, including PSPC1, NONO, and SFPQ. Under resting conditions, the complex is often associated with nuclear paraspeckles, but upon sensing foreign viral DNA or damaged host DNA, it undergoes structural remodeling and interacts with the cGAS-STING pathway. This remodeling facilitates the recruitment and phosphorylation of Interferon Regulatory Factor 3 (IRF3), which then drives the expression of type I interferons and other antiviral cytokines. Beyond its role in defending against viruses like KSHV and HIV-2, the HDP-RNP complex is implicated in the pathogenesis of autoimmune disorders and various cancers where its components promote tumor metastasis and survival. Therapeutic approaches currently focus on modulating individual subunits of the complex, such as using DNA-PK inhibitors or antisense oligonucleotides against NEAT1, to either temper autoimmune inflammation or enhance anti-tumor immunity.

Other names

HDP-RNP complexHEXIM1-NEAT1-DNA-PK complexHEXIM1-DNA-PK-paraspeckle-RNPHEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein

Functions as a nuclear scaffold and platform for DNA sensing that mediates the phosphorylation of IRF3 and subsequent induction of type I interferons upon detection of foreign or aberrant DNA.