Transfected DNA is targeted by STING-mediated restriction

Area of Science:

• Molecular Biology
• Immunology
• Cell Biology

Background:

• DNA transfection is a common method for gene delivery, but it can trigger innate immune responses.
• The precise impact of these responses on the expression of transfected DNA remains unclear.
• STING (stimulator of interferon genes) is a key mediator of innate immunity, responding to various nucleic acid stimuli.

Purpose of the Study:

• To investigate the role of STING in regulating gene expression from double-stranded DNA introduced via transfection.
• To elucidate the mechanisms underlying STING-mediated effects on transfected DNA.

Main Methods:

• Overexpression of STING and knockdown of endogenous STING using RNA interference in cultured cells.
• Analysis of gene expression from transfected double-stranded DNA.
• Assessment of mRNA levels and interferon-beta production.

Main Results:

• Overexpressed STING significantly repressed gene expression from transfected DNA.
• Knockdown of endogenous STING enhanced gene expression from transfected DNA.
• STING-mediated repression was specific to episomal DNA and did not affect chromosomal or integrated genes.
• Repression correlated with reduced mRNA levels and was partially dependent on STING-induced interferon-beta.

Conclusions:

• STING acts as a cellular defense mechanism that restricts gene expression from episomal double-stranded DNA.
• This STING-mediated restriction is independent of DNA topology, promoter, or origin.
• The findings reveal a novel role for STING in controlling the fate of transfected DNA.