A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the Saccharomyces cerevisiae Elongator complex.
Bottom Line: Since these modifications are required for the tRNAs to function efficiently, a translation defect caused by hypomodified tRNAs may therefore underlie the variety of phenotypes associated with Elongator dysfunction.The Elp1 carboxy-terminal domain contains a highly conserved arginine/lysine-rich region that resembles a nuclear localization sequence (NLS).Thus the conserved basic region in Elp1 may be essential for tRNA wobble uridine modification by acting as tRNA binding motif.
Affiliation: Centre for Gene Regulation & Expression, College of Life Sciences, MSI/WTB Complex, University of Dundee, Dundee, DD1 5EH, Scotland, UK.Show MeSH
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Mentions: The conserved basic region in Elp1 is essential for tRNA wobble uridine modification but despite being capable of functioning as an NLS, it does not appear to influence the distribution of the Elp1 between the nucleus and cytoplasm and is not required for overall assembly of the Elongator complex. In keeping with Elongator's role in tRNA wobble uridine modification, it was recently shown by electrophoretic mobility shift assay (EMSA) that the Elp4–6 hexameric subcomplex of Elongator directly binds tRNAGlu(UUC), consistent with a direct role for Elongator in tRNA binding and subsequent modification (Glatt et al., 2012). Since the basic region in Elp1 was clearly important for Elongator function we hypothesized that it could be involved in binding tRNA molecules to the Elp1–3 subcomplex for wobble uridine modification, given that the Elp3 subunit within this subcomplex is the most likely candidate for carrying out the modification reaction. Elp1 was therefore analysed for potential RNA binding sites using the binding prediction program BindN+, which predicts RNA binding regions from primary sequence based on the properties of RNA binding residues from known structures (Wang and Brown, 2006). This analysis highlighted the conserved carboxy-terminal basic region in both yeast and human Elp1 as being likely to bind RNA (Fig. 6A), consistent with the notion that it may be required for tRNA binding. Such a role might therefore explain the profound consequences of the elp1–KR9A allele on Elongator function.
Affiliation: Centre for Gene Regulation & Expression, College of Life Sciences, MSI/WTB Complex, University of Dundee, Dundee, DD1 5EH, Scotland, UK.