Research Departments & Organizations
Our major interests focus on the mechanism and evolution of aminoacyl-tRNA synthesis and the expansion of the genetic code. Currently twenty-two cotranslationally inserted amino acids (including selenocysteine and pyrrolysine) are known to occur in proteins. The synthesis of this set of amino-acyl-tRNAs is very diverse in nature, relying on direct acylation of tRNAs by aminoacyl-tRNA synthetases (as predicted by Crick’s adaptor hypothesis) and also on recently discovered, novel mechanisms of pre-translational tRNA-dependent amino acid modification. The latter process is related to tRNA-dependent amino acid biosynthesis (e.g., asparagine and cysteine), the sole route to these amino acids in many bacteria and archaea. These processes also enable us to synthesize proteins containing unusual amino acid (e.g., phosphoserine and pyrrolysine).
Specialized Terms: Aminoacyl-tRNA Synthesis; Functional Genomics; Life Science Biological; Mechanism of Translation
Extensive Research Description
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 22nd 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-tRNACys, the required intermediate in Cys-tRNA formation in methanogenic archaea. Based on similar enzymology, O-phosphoseryl-tRNASec 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.
The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation.
Palioura S, Sherrer RL, Steitz TA, Söll D, Simonovic M. The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. Science (New York, N.Y.) 2009, 325:321-5. 2009
A cytidine deaminase edits C to U in transfer RNAs in Archaea.
Randau L, Stanley BJ, Kohlway A, Mechta S, Xiong Y, Söll D. A cytidine deaminase edits C to U in transfer RNAs in Archaea. Science (New York, N.Y.) 2009, 324:657-9. 2009
Pyrrolysyl-tRNA synthetase-tRNA(Pyl) structure reveals the molecular basis of orthogonality.
Nozawa K, O'Donoghue P, Gundllapalli S, Araiso Y, Ishitani R, Umehara T, Söll D, Nureki O. Pyrrolysyl-tRNA synthetase-tRNA(Pyl) structure reveals the molecular basis of orthogonality. Nature 2009, 457:1163-7. 2009
Life without RNase P.
Randau L, Schröder I, Söll D. Life without RNase P. Nature 2008, 453:120-3. 2008
Mammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import.
Rubio MA, Rinehart JJ, Krett B, Duvezin-Caubet S, Reichert AS, Söll D, Alfonzo JD. Mammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105:9186-91. 2008
Quality control despite mistranslation caused by an ambiguous genetic code.
Ruan B, Palioura S, Sabina J, Marvin-Guy L, Kochhar S, Larossa RA, Söll D. Quality control despite mistranslation caused by an ambiguous genetic code. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105:16502-7. 2008