Alu RNA

Alu RNA is a non-coding RNA molecule transcribed from Alu elements, which are short interspersed nuclear elements (SINEs) that comprise approximately 11% of the human genome (Ambati et al., Nature, 2011). Under normal physiological conditions, Alu RNA levels are tightly regulated by the enzyme DICER1, which degrades these transcripts to prevent cellular toxicity (Kaneko et al., Nature, 2011). However, the pathological accumulation of Alu RNA—often resulting from DICER1 deficiency—triggers the NLRP3 inflammasome and subsequent cell death via pyroptosis (Fowler et al., Science, 2014). This mechanism is a primary driver of retinal pigment epithelium (RPE) degeneration in geographic atrophy, an advanced form of age-related macular degeneration (AMD) (Kerur et al., Nature Medicine, 2018). Therapeutic interventions currently under investigation include the use of nucleoside reverse transcriptase inhibitors (NRTIs) and their derivatives, known as kamuvudines, which block the inflammatory signaling induced by Alu RNA (Fowler et al., Science, 2014; Gelfand et al., PNAS, 2023). Additionally, antisense oligonucleotides are being explored to directly reduce Alu RNA concentrations in target tissues. Targeting Alu RNA represents a novel approach to treating sterile inflammatory diseases by addressing the "dark matter" of the genome.

Other names

Alu element transcriptAlu repeat RNASINE RNAShort Interspersed Nuclear Element RNA

Inhibition of Alu RNA-induced NLRP3 inflammasome activation and P2X7 receptor signaling, or direct degradation of Alu transcripts via antisense oligonucleotides (Fowler et al., Science, 2014; Kerur et al., Nature Medicine, 2018).