Elp3

Elp3, also known as Elongator complex protein 3, is a conserved enzymatic component of the multiprotein complex called Elongator. The Elongator complex plays a critical role in transcriptional elongation by RNA polymerase II and in the modification of tRNA molecules, specifically in the addition of a 5‑hydroxyl group at the wobble position of uridine residues. Elp3 encodes a protein that possesses a Rossmann fold typical of SAM-dependent methyltransferases. Unlike other methyltransferases, Elp3 utilizes acetyl-coenzyme A as a donor for acetylation at the tRNA wobble uridine, thus facilitating proper decoding during protein synthesis. In Saccharomyces cerevisiae, Elp3 is essential for growth under stress conditions and for the expression of genes involved in the unfolded protein response. In mammals, mutations in the ELP3 gene have been linked to neurodevelopmental disorders and age‑related neurodegeneration due to impaired tRNA modification and translational fidelity. Structural studies have shown a C‑terminal helix‑turn‑helix domain that mediates subunit interactions within the Elongator complex. Functional assays demonstrate that loss of Elp3 activity triggers defects in histone acetylation at promoters of stress‑response genes, revealing a dual role in transcriptional regulation and post‑transcriptional modification. Throughout evolution, Elp3 is broadly conserved across eukaryotes, underscoring its fundamental contributions to RNA biology and cell physiology.