Pathogenic mitochondrial RNA (mtRNA)

Pathogenic mitochondrial RNA refers to a class of mitochondrial-derived RNA molecules that contribute to disease through genetic mutations, aberrant expression, or mislocalization. This category includes mutated mitochondrial messenger RNA (mt-mRNA), transfer RNA (mt-tRNA), and ribosomal RNA (mt-rRNA) resulting from mitochondrial DNA (mtDNA) mutations, which impair oxidative phosphorylation and lead to mitochondrial diseases such as MELAS and MERRF [2.2.1, 2.2.2]. It also encompasses antisense non-coding mitochondrial RNAs (ASncmtRNAs), which are uniquely expressed in proliferating cancer cells and serve as targets for antisense therapy to induce selective apoptosis [3.1.4, 3.3.1]. Furthermore, double-stranded mitochondrial RNA (ds-mtRNA) can accumulate and escape into the cytosol under stress, acting as a damage-associated molecular pattern (DAMP) that triggers innate immune responses via the cGAS-STING and RIG-I-like receptor pathways [2.1.2, 2.1.4]. Therapeutic strategies targeting these RNAs primarily utilize antisense oligonucleotides (ASOs) to degrade specific pathogenic transcripts or modulate heteroplasmy levels to restore mitochondrial function [2.3.2, 3.2.3].

Other names

Mutated mitochondrial RNAAntisense non-coding mitochondrial RNAASncmtRNAMitochondrial double-stranded RNAmt-dsRNAMitochondrial DAMPs

Antisense oligonucleotide-mediated RNA degradation (RNase H-mediated), reduction of deleterious heteroplasmy, and inhibition of pro-survival markers (e.g., survivin) to induce apoptosis in target cells.