ABSTRACT
Nascent ribosomal 60S subunits undergo the last maturation steps in the cytoplasm. The last one involves removing the anti-association factor eIF6 from the 60S ribosomal surface by the joint action of the Elongation Factor-like 1 (EFL1) GTPase and the SBDS protein. Herein, we studied the evolutionary relationship of the EFL1 and EF-2 protein families and the functional conservation within EFL1 orthologues. Phylogenetic analysis demonstrated that the EFL1 proteins are exclusive of eukaryotes and share an evolutionary origin with the EF-2 and EF-G protein families. EFL1 proteins originated by gene duplication from the EF-2 proteins and specialized in ribosome maturation while the latter retained their function in translation. Some organisms have more than one EFL1 protein resulting from alternative splicing, while others are encoded in different genes originated by gene duplication. However, the function of these alternative EFL1 proteins is still unknown. We performed GTPase activity and complementation assays to study the functional conservation of EFL1 homologs alone and together with their SBDS counterparts. None of the orthologues or cross-species combinations could replace the function of the corresponding yeast EFL1â¢SBDS binomial. The complementation of SBDS interspecies chimeras indicates that domain 2 is vital for its function together with EFL1 and the 60S subunit. The results suggest a functional species-specificity and possible co-evolution between EFL1, SBDS, and the 60S ribosomal subunit. These findings set the basis for further studies directed to understand the molecular evolution of these proteins and their impact on ribosome biogenesis and disease.
