Elongator

Elongator, or the elongator complex, is a conserved eukaryotic multi-subunit protein complex implicated in two major cellular processes: transcriptional elongation by RNA polymerase II and the modification of transfer RNAs. It was named for its initial identification in studies of transcriptional elongation, but later research revealed a distinct role in tRNA modification as well. The dual involvement in transcription and translation has made elongator a focus of studies on gene expression regulation and protein synthesis.

In yeast, the elongator complex comprises six subunits: Elp1, Elp2, Elp3, Elp4, Elp5, and Elp6. In metazoans these subunits are conserved and commonly referred to as ELP1 through ELP6. Elp3 contains the catalytic histone acetyltransferase–like domain, while Elp1–Elp2–Elp4–Elp5–Elp6 contribute to complex assembly, stability, and recruitment to chromatin or other cellular sites. The complex can associate with additional factors, such as Kti12 in some species, which influence its activity.

Functionally, elongator engages in transcriptional elongation by associating with RNA polymerase II and promoting chromatin modifications that facilitate extended transcription. Separately, it participates in tRNA modification by catalyzing the formation of certain wobble uridine modifications, such as mcm5s2U, which enhance codon–anticodon pairing and translational efficiency. While these roles may be mechanistically distinct, they share the same multi-subunit complex, illustrating how elongator links transcriptional regulation with translation.

In humans, mutations in ELP1 (also known as IKBKAP) cause familial dysautonomia, a neurodevelopmental disorder. Alterations in other elongator subunits have been associated with neurological conditions and cancer, underscoring the biological importance of the complex. The elongator complex is considered highly conserved from yeast to humans and remains a subject of ongoing research into its diverse cellular functions.