Mitochondrial RNA (mtRNA) (mtRNA)

Mitochondrial RNA (mtRNA) refers to the set of RNA molecules encoded by the mitochondrial DNA (mtDNA), comprising 13 messenger RNAs (mRNAs), 2 ribosomal RNAs (rRNAs), and 22 transfer RNAs (tRNAs) (Mercer et al., 2011). These molecules are essential for the synthesis of core subunits of the oxidative phosphorylation (OXPHOS) system, which generates the majority of cellular ATP (Hällberg & Larsson, 2014). mtRNA is transcribed as long polycistronic units from both the heavy and light strands of mtDNA and undergoes complex processing, including endonucleolytic cleavage and polyadenylation, within specialized structures called mitochondrial RNA granules (Antonicka & Shoubridge, 2015). Dysregulation of mtRNA metabolism is a hallmark of primary mitochondrial diseases and has been increasingly implicated in cancer progression, where metabolic reprogramming is required for tumor growth (Zong et al., 2016). Therapeutic targeting of mtRNA is an emerging field, utilizing small molecule inhibitors of mitochondrial transcription (e.g., IMT1) to starve cancer cells of energy or antisense oligonucleotides to correct mutations in mitochondrial transcripts (Bonekamp et al., 2020; Wang et al., 2021). However, the high degree of conservation between mitochondrial and bacterial ribosomes leads to off-target effects for many antibiotics, and the double-membrane structure of the mitochondria remains a significant barrier for drug delivery (Gorman et al., 2016).

Other names

mt-RNAMitochondrial transcriptMitochondrial messenger RNAMitochondrial ribosomal RNAMitochondrial transfer RNA

Inhibition of mitochondrial transcription via POLRMT inhibition, disruption of mitochondrial translation by binding to mitochondrial ribosomal RNA, and depletion of mitochondrial RNA transcripts.