Inosine in RNA (I)

Inosine in RNA is a critical post-transcriptional modification generated by the hydrolytic deamination of adenosine, a process catalyzed by Adenosine Deaminase Acting on RNA (ADAR) enzymes. Because inosine is read as guanosine (G) by the cellular translation and splicing machinery, A-to-I editing can fundamentally alter the genetic code at the transcript level, leading to protein recoding and altered RNA processing. Beyond its role in transcript diversity, inosine serves as a vital 'self' signal for the innate immune system; the presence of inosine in double-stranded RNA (dsRNA) prevents the activation of the MDA5 receptor, thereby suppressing an interferon-mediated immune response against endogenous transcripts. In therapeutic contexts, 'Inosine in RNA' is targeted in two primary ways: first, by inhibiting ADAR1 to increase 'un-edited' dsRNA in cancer cells to stimulate anti-tumor immunity; and second, by using RNA-guided tools to site-specifically introduce inosine to correct G-to-A mutations in genetic diseases. This dual role makes the regulation of inosine levels a high-priority area for both oncology and precision genetic medicine.

Other names

A-to-I RNA editingInosine modificationHypoxanthine riboside in RNAInosine-containing RNA

Modulation of ADAR enzyme activity to alter inosine levels, site-specific recruitment of endogenous ADAR for RNA base editing, and inhibition of A-to-I conversion to stimulate innate immune sensing in tumors.