Mitochondrial mRNA modification

Polyadenylation at the 3' ends of mitochondrial mRNAs is produced by MTPAP (also called PAPD1), a dimeric polyadenylate polymerase located in both the cytosol and the mitochondrial matrix (Nagaike et al. 2005, Slomovic and Schuster 2008, Bai et al. 2011, Wilson et al. 2014, reviewed in Chang and Tong 2012). Like the polyadenylate tails of cytoplasmic mRNAs, the mitochondrial polyadenylate tails appear to stabilize the mRNAs, however, mitochondrial polyadenylate tails (~40-50 adenylate residues) are shorter than those observed in the cytosol (~250 adenylate residues) (reviewed in Boreikaitė and Passmore 2023). MTPAP may also catalyze polyuridylation.

Pseudouridylation in mitochondria is catalyzed by a large protein complex, the mitochondrial pseudouridylation module, that contains the pseudouridine synthases RPUSD3, RPUSD4, and TRUB2. RPUSD4 pseudouridylates rRNA and tRNA while either RPUSD3 or TRUB2 are capable of pseudouridylating uridine-390 of MT-CO1 mRNA and uridine-697 of MT-CO3 mRNA. Depletion of either RPUSD3 or TRUB2 caused a reduction in mitochondrial translation.

In mitochondria, methylation of the N1 position of adenosine residues in mRNAs is catalyzed by the methyltransferase TRMT61B, which methylates adenosine residues in the MT-ND1, MT-CO1, MT-CO2, MT-CO3, MT-ND4L, and MT-CYB mRNAs. N1-methyladenosine in mitochondrial mRNAs causes ribosome stalling and reduced translation.