TRNA-derived G-quadruplex protects motor neurons.

Abstract

Although not generally appreciated, the first 3D visualization of a nucleic acid was provided by the crystal structures of yeast phenylalanine transfer RNA (tRNA) (1, 2). [The DNA structure determined in the 1950s was a low-resolution fiber-diffraction–based model (3).] It was interesting to see that the L-shaped tRNA molecule is maintained by both Watson–Crick and non-Watson–Crick types of base interactions. These types include Hoogsteen base pairs that use the N7-C6 face of a purine to make hydrogen-bonding interactions. The scheme of the Hoogsteen base pairing also allows the formation of a planar interaction with four guanine residues, known as G-tetrad or G-quartet (Fig. 1A). Despite the fact that the G-tetrad interaction was first proposed over 50 y ago (4), demonstration of its biological significance was much later and not until it was found in the structure of telomeres (5⇓–7). The 3′-end overhang of vertebrate telomeres are rich in guanines and consist of many TTAGGG repeats that can spontaneously fold into four-stranded DNA structures with two or more G-tetrads stacking on top of each other. Functionally, formation of this unique structure—named G-quadruplex—plays a major regulatory role in telomere maintenance (8). Since then, G-quadruplex structures became widely noted to be present throughout the genome and …