Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide-quadruplex complex.

Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex-protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes.

Formation of a stacked dimeric G-quadruplex containing bulges by the 5'-terminal region of human telomerase RNA (hTERC).

We investigate the structure formed by the first 18-nt of the 5'-terminal region of the human telomerase RNA (hTERC or hTR) using gel electrophoresis and UV, CD, and NMR spectroscopy. Our data suggest that this 18-nt sequence, r(GGGUUGCGGAGGGUGGGC), can form a stacked dimeric G-quadruplex in potassium solution. The two subunits, each being a three-layer parallel-stranded G-quadruplex with a cytosine bulge, are stacked at their 5'-end.

Structure of human telomeric RNA (TERRA): stacking of two G-quadruplex blocks in K(+) solution.

Telomeric repeat-containing RNAs (TERRA) are transcription products of the telomeres. Human TERRA sequences containing UUAGGG repeats can form parallel-stranded G-quadruplexes. The stacking interaction of such structures was shown to be important for ligand targeting and higher-order arrangement of G-quadruplexes in long TERRA sequences.

Structure of long human telomeric RNA (TERRA): G-quadruplexes formed by four and eight UUAGGG repeats are stable building blocks.

The discovery of long RNA transcripts of telomeric repeats (TERRA) and their potential to form G-quadruplexes stimulated studies on the possible arrangements of G-quadruplexes along TERRA. Here we performed ribonuclease protection assay to investigate the structures formed by long human TERRA. We found that G-quadruplexes comprising four and eight UUAGGG repeats were most resistant to RNase T1 digestion, presumably with the former adopting an all-parallel-stranded propeller-type conformation and the latter forming a structure with two tandemly stacked G-quadruplex subunits each containing three G-tetrad layers.

Structure of propeller-type parallel-stranded RNA G-quadruplexes, formed by human telomeric RNA sequences in K+ solution.

Very recent studies showed that mammalian telomeres were transcribed into telomeric-repeat-containing RNAs and suggested that these RNA molecules were biologically important. Here we report on a structural study of RNA G-quadruplexes formed by human telomeric RNA sequences in K(+) solution. Our data indicated that these sequences formed propeller-type parallel-stranded RNA G-quadruplexes.