Dieter Soll, PhD

Research in the Söll laboratory centers around functional genomic investigations that explore the translation of the genetic code with canonical and modified amino acids. We are studying archaeal, bacterial and eukaryotic systems in a multidisciplinary approach that includes genetics, biochemistry, enzymology, structural analysis, and molecular biology.

The ancient essential process of ribosomal protein synthesis requires twenty sets of aminoacyl-tRNAs, one for each canonical amino acid, for the correct transmission of the genetic information. Since Crick proposed his adaptor hypothesis it was commonly accepted that all organisms or organelles possess twenty aminoacyl-tRNA synthetases, each enzyme specific for attaching one amino acid to tRNA. It is now clear that aminoacyl-tRNA formation is far more varied, as the biosynthetic routes to asparaginyl-tRNA, glutaminyl-tRNA, lysyl-tRNA and cysteinyl-tRNA vary greatly in nature. For instance, the amide aminoacyl-tRNAs (Asn-tRNA and Gln-tRNA) can be formed by two redundant mechanisms, direct acylation or pre-translational amino acid modification by amidation. Thus, the routes to these tRNAs differ not only in the three domains of life but also vary among organelles. These transamidation enzymes appear to have evolved by recruitment of amino acid metabolizing enzymes. This possible evolutionary link between protein synthesis and amino acid biosynthesis is further highlighted by the discovery that tRNA-dependent amidation of aspartate appears to be the sole route to asparagine synthesis in most bacteria.

The discovery of a non-canonical lysyl-tRNA synthetase gave the first clues on the aminoacylation of pyrrolysine, the 22^nd cotranslationally inserted amino acid. Formation of pyrrolysyl-tRNA in the Methanosarcinaceae is catalyzed by an aminoacyl-tRNA synthetase solely specific for a modified amino acid. An analogous enzyme forms O-phosphoseryl-tRNA^Cys, the required intermediate in Cys-tRNA formation in methanogenic archaea. Based on similar enzymology, O-phosphoseryl-tRNA^Sec is the required precursor for synthesis in archaea and eukaryotes of selenocysteine, the 21st cotranslationally inserted amino acid.

New challenges to our understanding of tRNA biosynthesis and the role of the RNA intron emerge from the finding that the deep-rooted organism Nanoarcheaon equitansmakes functional tRNA from encoded half-genes.