Publications

• How U38, 39, and 40 of many tRNAs become the targets for pseudouridylation by TruA.

  Hur S., Stroud R.M.

  Translational accuracy and efficiency depend upon modification of uridines in the tRNA anticodon stem loop (ASL) by a highly conserved pseudouridine synthase TruA. TruA specifically modifies uridines at positions 38, 39, and/or 40 of tRNAs with highly divergent sequences and structures through a p ... >> More

  Translational accuracy and efficiency depend upon modification of uridines in the tRNA anticodon stem loop (ASL) by a highly conserved pseudouridine synthase TruA. TruA specifically modifies uridines at positions 38, 39, and/or 40 of tRNAs with highly divergent sequences and structures through a poorly characterized mechanism that differs from previously studied RNA-modifying enzymes. The molecular basis for the site and substrate "promiscuity" was studied by determining the crystal structures of E. coli TruA in complex with two different leucyl tRNAs in conjunction with functional assays and computer simulation. The structures capture three stages of the TruA*tRNA reaction, revealing the mechanism by which TruA selects the target site. We propose that TruA utilizes the intrinsic flexibility of the ASL for site promiscuity and also to select against intrinsically stable tRNAs to avoid their overstabilization through pseudouridylation, thereby maintaining the balance between the flexibility and stability required for its biological function. << Less

  Mol. Cell 26:189-203(2007) [PubMed] [EuropePMC]

• The structural basis for tRNA recognition and pseudouridine formation by pseudouridine synthase I.

  Foster P.G., Huang L., Santi D.V., Stroud R.M.

  Pseudouridine synthases catalyze the isomerization of specific uridines to pseudouridine in a variety of RNAs, yet the basis for recognition of the RNA sites or how they catalyze this reaction is unknown. The crystal structure of pseudouridine synthase I from Escherichia coli, which, for example, ... >> More

  Pseudouridine synthases catalyze the isomerization of specific uridines to pseudouridine in a variety of RNAs, yet the basis for recognition of the RNA sites or how they catalyze this reaction is unknown. The crystal structure of pseudouridine synthase I from Escherichia coli, which, for example, modifies positions 38, 39 and/or 40 in tRNA, reveals a dimeric protein that contains two positively charged, RNA-binding clefts along the surface of the protein. Each cleft contains a highly conserved aspartic acid located at its center. The structural domains have a topological similarity to those of other RNA-binding proteins, though the mode of interaction with tRNA appears to be unique. The structure suggests that a dimeric enzyme is required for binding transfer RNA and subsequent pseudouridine formation. << Less

  Nat. Struct. Biol. 7:23-27(2000) [PubMed] [EuropePMC]