RNA Hydration:  A Detailed Look^,

Abstract

The crystal structure of the RNA duplex [r(CCCCGGGG)]2 has been refined to 1.46 A resolution with room temperature synchrotron diffraction data. This represents the highest resolution reported to date for an all-RNA oligonucleotide and is well beyond the best resolution ever achieved with an A-form DNA duplex. The analysis of the ordered hydration around the octamer duplex reveals conserved regular arrangements of water molecules in both grooves. In the major groove, all located first shell water molecules can be fitted into a pattern that is repeated through all eight base pairs, involves half the phosphate oxygens, and joins the two strands. In the minor groove, roughly across its narrowest dimension, tandem water molecules link the 2'-hydroxyl groups of adjacent nucleotides in base-pair steps in a similarly regular fashion. The structure provides evidence for an important role of the 2'-hydroxyl groups in the thermodynamic stabilization of RNA, beyond their known functions of locking the sugar pucker and mediating 3' --> 5' intrastrand O2'...O4' hydrogen bonds. The ribose 2'-hydroxyls lay the foundation for the enthalpic stability of the RNA relative to the DNA duplex, both as a scaffold for the water network in the minor groove and through their extensive individual hydration.

RNA hydration: three nanoseconds of multiple molecular dynamics simulations of the solvated tRNA Asp anticodon hairpin 1 1Edited by J. Karn

“…Recently, from X-ray structures of RNA duplexes, it has been shown, in agreement with earlier studies of the hydration of tRNAs , that water molecules may establish one or multiple water bridges between 2 H -hydroxyl groups and base atoms (Egli et al, 1996;Wahl et al, 1996). The present data suggest that such hydration patterns may result from frequently exchanging water molecules instead of single water molecules with long residence times.…”

“…The screening of the O 4 H atoms, associated with an HB% of 64% for the H O2 H atoms, is consistent with the absence of long-lived hydrogen bonds between the 2 H -hydroxyl group and the O 4 H atom of the next ribose on the 3 H side, as noted earlier (Auf®nger et al, 1997). Thus, the hydroxyl group prefers to be an hydrogen bond donor towards water molecules than towards the nearby O 4 H atom (Egli et al, 1996). The ribose hydroxyl O 2 H atoms are hydrated to approximately 100%, satisfying only half of their hydrogen bond acceptor potential for sterical reasons.…”

“…The authors suggested that intrastrand hydrogen bonds between ribose O 2 H and O 4 H atoms are weak and may not account for signi®cant stabilization of RNA helices. They proposed that water molecules are much better H-bond acceptors than ribose O 4 H atoms (Egli et al, 1996). This conclusion is corroborated by NMR experiments, which have suggested that the 2 H -hydroxyl proton is hydrogen bonded to a water molecule (Bolton & Kearns, 1978).…”

“…In a recent structure of the r(CCCCGGGG) 2 octamer, where all water molecules in the ®rst hydration shell could be localized, the 2 H -hydroxyl groups were observed to be heavily hydrated (Egli et al, 1996). The authors suggested that intrastrand hydrogen bonds between ribose O 2 H and O 4 H atoms are weak and may not account for signi®cant stabilization of RNA helices.…”

“…In helical duplexes, owing to the periodicity of the contacts between water and each repeating unit, speci®c hydration patterns are frequently observed. For example, a recent analysis of the highresolution crystal structure of the regular r(CCCCGGGG) RNA duplex reveals a repetitive arrangement of water molecules around base-pairs and along the backbone (Egli et al, 1996). However, for non-periodic structures like singlestranded and loop regions, our knowledge of hydration motifs is scantier because of the limited number and the low resolution of the available crystallographic data.…”