Structure of an unusually stable RNA hairpin

Journal Article · Tue Apr 02 04:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00227a016· OSTI ID:5398100

Varani, G; Cheong, Chaejoon; Tinoco, I Jr ^[1]

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1. Univ. of California, Berkeley (USA)

The structure of a very common RNA hairpin, 5{prime}GGAC(UUCG)GUCC, has been determined in solution by NMR spectroscopy. The loop sequence, UUCG, occurs exceptionally often in ribosomal and other RNAs, and may serve as a nucleation site for RNA folding and as a protein recognition site. Reverse transcriptase cannot read through this loop, although it normally transcribes RNA secondary structure motifs. A hairpin with that loop displays unusually high thermodynamic stability; its stability decreases when conserved nucleotides are mutated. The three-dimensional structure for the hairpin was derived from interproton distances and scalar coupling constants determined by NMR using distance geometry, followed by restrained energy minimization. The structure was well-defined despite the conservative use of interproton distances, by constraining the backbone conformation by means of scalar coupling measurements. A mismatch G{center dot}U base pair, with syn-guanosine, closes the stem. This hairpin has a loop of only two nucleotides; both adopt C{sub 2{prime}}-endo sugar pucker. A sharp turn in the phosphodiester backbone is stabilized by a specific cytosine-phosphate contact, probably a hydrogen bond, and by stacking of the cytosine nucleotide on the G{center dot}U base pair. The structural features of the loop can explain the unusual thermodynamic stability of this hairpin and its sensitivity to mutations of loop nucleotides.

• DOE Contract Number: FG03-86ER60406
• OSTI ID: 5398100
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:13; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
BARYONS
CHEMICAL SHIFT
ELEMENTARY PARTICLES
FERMIONS
GEOMETRY
HADRONS
MAGNETIC RESONANCE
MATHEMATICS
MOLECULAR STRUCTURE
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
NUCLEOTIDES
ORGANIC COMPOUNDS
OVERHAUSER EFFECT
PROTONS
RESONANCE
RNA