Rabbit Anti-Human ELAC2 (a.a. 88-190) Polyclonal antibody

The human mitochondrial genome encodes RNA components of its own translational machinery to produce the 13 mitochondrial-encoded subunits of the respiratory chain. Nuclear-encoded gene products are essential for all processes within the organelle, including RNA processing. Transcription of the mitochondrial genome generates large polycistronic transcripts punctuated by the 22 mitochondrial (mt) tRNAs that are conventionally cleaved by the RNase P-complex and the RNase Z activity of ELAC2 at 5' and 3' ends, respectively. We report the identification of mutations in ELAC2 in five individuals with infantile hypertrophic cardiomyopathy and complex I deficiency. We observed accumulated mtRNA precursors in affected individuals muscle and fibroblasts. Although mature mt-tRNA, mt-mRNA, and mt-rRNA levels were not decreased in fibroblasts, the processing defect was associated with impaired mitochondrial translation. Complementation experiments in mutant cell lines restored RNA processing and a yeast model provided additional evidence for the disease-causal role of defective ELAC2, thereby linking mtRNA processing to human disease.

Ribosome-associated quality control (RQC) disassembles aberrantly stalled translation complexes to recycle or degrade the constituent parts. A key step of RQC is the cleavage of P-site tRNA by the endonuclease ANKZF1 (Vms1 in yeast) to release incompletely synthesized polypeptides from ribosomes for degradation. Re-use of the cleaved tRNA for translation requires re-addition of the universal 3'CCA nucleotides removed by ANKZF1. Here, we show that ELAC1 is both necessary and sufficient to remove the 2',3'-cyclic phosphate on ANKZF1-cleaved tRNAs to permit CCA re-addition by TRNT1. ELAC1 activity is optimized for tRNA recycling, whereas ELAC2, the essential RNase Z isoform in eukaryotes, is required to remove 3' trailers during tRNA biogenesis. Cells lacking ELAC1 specifically accumulate unrepaired tRNA intermediates upon the induction of ribosome stalling. Thus, optimal recycling of ANKZF1-cleaved tRNAs in vertebrates is achieved through the duplication and specialization of a conserved tRNA biosynthesis enzyme.