Mitochondrial mRNA modification

Stable Identifier
R-HSA-9937008
Type
Pathway
Species
Homo sapiens
ReviewStatus
3/5
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Mitochondrial mRNA modification
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Mitochondrial mRNAs contain polyadenylation, pseudouridylation, and N1-adenosine methylation, posttranscriptional modifications that are catalyzed by proteins encoded in the nucleus (reviewed in Chrzanowska-Lightowlers and Lightowlers 2024).
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 (Nagaike et al. 2005), 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 (Arroyo et al. 2016, Antonicka et al. 2017). 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 (Carlile et al. 2019, Antonicka et al. 2017). Depletion of either RPUSD3 or TRUB2 caused a reduction in mitochondrial translation (Antonicka et al. 2017).
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 (Li et al. 2017). N1-methyladenosine in mitochondrial mRNAs causes ribosome stalling and reduced translation (Li et al. 2017).
Literature References
PubMed ID Title Journal Year
18083837 Stable PNPase RNAi silencing: its effect on the processing and adenylation of human mitochondrial RNA

Slomovic, S, Schuster, G

RNA 2008
21292163 Structural basis for dimerization and activity of human PAPD1, a noncanonical poly(A) polymerase

Bai, Y, Srivastava, SK, Chang, JH, Manley, JL, Tong, L

Mol Cell 2011
27667664 A Genome-wide CRISPR Death Screen Identifies Genes Essential for Oxidative Phosphorylation

Arroyo, JD, Jourdain, AA, Calvo, SE, Ballarano, CA, Doench, JG, Root, DE, Mootha, VK

Cell Metab 2016
37001138 3'-End Processing of Eukaryotic mRNA: Machinery, Regulation, and Impact on Gene Expression

Boreikaitė, V, Passmore, LA

Annu Rev Biochem 2023
22172994 Mitochondrial poly(A) polymerase and polyadenylation

Chang, JH, Tong, L

Biochim Biophys Acta 2012
25008111 A human mitochondrial poly(A) polymerase mutation reveals the complexities of post-transcriptional mitochondrial gene expression

Wilson, WC, Hornig-Do, HT, Bruni, F, Chang, JH, Jourdain, AA, Martinou, JC, Falkenberg, M, Spåhr, H, Larsson, NG, Lewis, RJ, Hewitt, L, Baslé, A, Cross, HE, Tong, L, Lebel, RR, Crosby, AH, Chrzanowska-Lightowlers, ZM, Lightowlers, RN

Hum Mol Genet 2014
27974379 A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability

Antonicka, H, Choquet, K, Lin, ZY, Gingras, AC, Kleinman, CL, Shoubridge, EA

EMBO Rep 2017
31477916 mRNA structure determines modification by pseudouridine synthase 1

Carlile, TM, Martinez, NM, Schaening, C, Su, A, Bell, TA, Zinshteyn, B, Gilbert, WV

Nat Chem Biol 2019
15769737 Human mitochondrial mRNAs are stabilized with polyadenylation regulated by mitochondria-specific poly(A) polymerase and polynucleotide phosphorylase

Nagaike, T, Suzuki, T, Katoh, T, Ueda, T

J Biol Chem 2005
39385590 Mitochondrial RNA maturation

Chrzanowska-Lightowlers, ZM, Lightowlers, RN

RNA Biol 2024
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mRNA modification (0016556)
Authored
May, B  (2025-01-25)
Created
May, B  (2025-01-28)
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