5nfj

Structural highlights

Disease

[TM10C_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.

Function

[TM10C_HUMAN] Mitochondrial tRNA N(1)-methyltransferase involved in mitochondrial tRNA maturation (PubMed:18984158, PubMed:21593607, PubMed:23042678, PubMed:27132592). Component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and MRPP3, which cleaves tRNA molecules in their 5'-ends (PubMed:18984158). Together with HSD17B10/MRPP2, forms a subcomplex of the mitochondrial ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions that are independent of the ribonuclease P activity (PubMed:23042678, PubMed:29040705). The MRPP1-MRPP2 subcomplex catalyzes the formation of N(1)-methylguanine and N(1)-methyladenine at position 9 (m1G9 and m1A9, respectively) in tRNAs; TRMT10C/MRPP1 acting as the catalytic N(1)-methyltransferase subunit (PubMed:23042678). The MRPP1-MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'-end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by ELAC2, retains the tRNA product after ELAC2 processing and presents the nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1 enzyme (PubMed:29040705). In addition to tRNA N(1)-methyltransferase activity, TRMT10C/MRPP1 also acts as a mRNA N(1)-methyltransferase by mediating methylation of adenosine residues at the N(1) position of MT-ND5 mRNA (PubMed:29072297).^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Holzmann J, Frank P, Loffler E, Bennett KL, Gerner C, Rossmanith W. RNase P without RNA: identification and functional reconstitution of the human mitochondrial tRNA processing enzyme. Cell. 2008 Oct 31;135(3):462-74. PMID:18984158 doi:S0092-8674(08)01135-5
2. ↑ Brzezniak LK, Bijata M, Szczesny RJ, Stepien PP. Involvement of human ELAC2 gene product in 3' end processing of mitochondrial tRNAs. RNA Biol. 2011 Jul-Aug;8(4):616-26. doi: 10.4161/rna.8.4.15393. Epub 2011 Jul 1. PMID:21593607 doi:http://dx.doi.org/10.4161/rna.8.4.15393
3. ↑ Vilardo E, Nachbagauer C, Buzet A, Taschner A, Holzmann J, Rossmanith W. A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase--extensive moonlighting in mitochondrial tRNA biogenesis. Nucleic Acids Res. 2012 Dec;40(22):11583-93. doi: 10.1093/nar/gks910. Epub 2012, Oct 5. PMID:23042678 doi:http://dx.doi.org/10.1093/nar/gks910
4. ↑ Metodiev MD, Thompson K, Alston CL, Morris AAM, He L, Assouline Z, Rio M, Bahi-Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rotig A, Taylor RW. Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies. Am J Hum Genet. 2016 May 5;98(5):993-1000. doi: 10.1016/j.ajhg.2016.03.010. Epub , 2016 Apr 28. PMID:27132592 doi:http://dx.doi.org/10.1016/j.ajhg.2016.03.010
5. ↑ Reinhard L, Sridhara S, Hallberg BM. The MRPP1/MRPP2 complex is a tRNA-maturation platform in human mitochondria. Nucleic Acids Res. 2017 Dec 1;45(21):12469-12480. doi: 10.1093/nar/gkx902. PMID:29040705 doi:http://dx.doi.org/10.1093/nar/gkx902
6. ↑ Safra M, Sas-Chen A, Nir R, Winkler R, Nachshon A, Bar-Yaacov D, Erlacher M, Rossmanith W, Stern-Ginossar N, Schwartz S. The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution. Nature. 2017 Nov 9;551(7679):251-255. doi: 10.1038/nature24456. Epub 2017 Oct 25. PMID:29072297 doi:http://dx.doi.org/10.1038/nature24456