Elongator and the role of its subcomplexes in human diseases

Abstract

The Elongator complex was initially identified in yeast, and a variety of distinct cellular functions have been assigned to the complex. In the last decade, several research groups focussed on dissecting its structure, tRNA modification activity and role in translation regulation. Recently, Elongator emerged as a crucial factor for various human diseases, and its involvement has triggered a strong interest in the complex from numerous clinical groups. The Elongator complex is highly conserved among eukaryotes, with all six subunits (Elp1-6) contributing to its stability and function. Yet, recent studies have shown that the two subcomplexes, namely the catalytic Elp123 and accessory Elp456, may have distinct roles in the development of different neuronal subtypes. This Commentary aims to provide a brief overview and new perspectives for more systematic efforts to explore the functions of the Elongator in health and disease.

Keywords: Elongator complex; Elp2; Elp4; Elp6; cancer; neurodevelopment; tRNA modification.

Figure 1. The effect of Elongator mutations in human diseases

Model of the eukaryotic Elongator complex highlighting one of its Elp123 lobes (surface representation) and the bound Elp456 (cartoon representation). The six subunits (Elp1‐6) are labelled and subunits with known clinical mutations are marked with an asterisk. Different cellular consequences of an aberrant tRNA modification activity for tumorigenesis (left) and neurodegenerative disease (right) are illustrated below.