Effects of Pseudouridylation on tRNA Hydration and Dynamics: a Theoretical Approach

Abstract

This chapter focuses on the structural implications resulting from the occurrence of this residue in tRNA and also presents an overview of the tRNA pseudouridylation sites. The principle of molecular dynamics (MD) resides in the numerical integration of the Newtonian equations of motion. The potential energy function contains several terms that account for covalent bond stretching, bond angle bending, harmonic dihedral bending, and nonbonded interactions including van der Waals and Coulombic terms. The residence time of this water molecule, which is consistently observed in several MD simulations, was estimated to be significantly longer than 500 ps. This water molecule forms an important structural link between the nucleotide backbone and the modified base and, thus, reduces the conformational mobility of the RNA close to the pseudouridylation site. Summarizing the preceding information suggests strongly that the main function of pseudouridylation close to the anticodon is to stabilize the structure of the loop by reducing its intrinsic dynamics, likely to avoid codon misreading. Pseudouridines are also important in ribosomal RNA and small nuclear RNA. It would not be surprising that in most structural contexts pseudouridines would stabilize rRNA and snRNA in a similar manner as in tRNA. In snRNA, the occurrence of pseudouridines in single-stranded regions may be required to improve their recognition features. Recent MD studies on the conformational behavior of 2'-OH groups in tRNA may be considered as a first approach toward the investigation of the roles of 2'-O-methyl groups.