Structural highlights
Disease
RNZ2_HUMAN Familial prostate cancer;Combined oxidative phosphorylation defect type 17. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
RNZ2_HUMAN Zinc phosphodiesterase, which displays mitochondrial tRNA 3'-processing endonuclease activity. Involved in tRNA maturation, by removing a 3'-trailer from precursor tRNA (PubMed:21593607). Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly (PubMed:24703694).[1] [2]
Publication Abstract from PubMed
Human elaC ribonuclease Z 2 (ELAC2) removes the 3' trailer of precursor transfer ribonucleic acid (pre-tRNA). Mutations in ELAC2 are highly associated with the development of prostate cancer and hypertrophic cardiomyopathy. However, the catalytic mechanism of ELAC2 remains unclear. We determined the cryogenic electron microscopy structures of human ELAC2 in various states, including the apo, pre-tRNA-bound and tRNA-bound states, which enabled us to identify the structural basis for its binding to pre-tRNA and cleavage of the 3' trailer. Notably, conformational rearrangement of the C-terminal helix was related to feeding of the 3' trailer into the cleavage site, possibly explaining why its mutations are associated with disease. We further used biochemical assays to analyse the structural effects of disease-related mutations of human ELAC2. Collectively, our data provide a comprehensive structural basis for how ELAC2 recruits pre-tRNA via its flexible arm domain and guides the 3' trailer of pre-tRNA into the active centre for cleavage by its C-terminal helix.
Structural insights into human ELAC2 as a tRNA 3' processing enzyme.,Xue C, Tian J, Chen Y, Liu Z Nucleic Acids Res. 2024 Nov 27;52(21):13434-13446. doi: 10.1093/nar/gkae1014. PMID:39494506[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Bogenhagen DF, Martin DW, Koller A. Initial steps in RNA processing and ribosome assembly occur at mitochondrial DNA nucleoids. Cell Metab. 2014 Apr 1;19(4):618-29. PMID:24703694 doi:10.1016/j.cmet.2014.03.013
- ↑ Xue C, Tian J, Chen Y, Liu Z. Structural insights into human ELAC2 as a tRNA 3' processing enzyme. Nucleic Acids Res. 2024 Nov 27;52(21):13434-13446. PMID:39494506 doi:10.1093/nar/gkae1014
