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Book of Abstracts: Albany 2003

category image Albany 2003
Conversation 13
Abstract Book
June 17-21 2003

UNCG or YNMG?

Stable hairpin loops are ubiquitous in RNA sequences; they are involved in the lower levels of the hierarchical folding of RNA and participate in tertiary interactions. An "extraordinarily stable" UUCG tetraloop is one of the best-studied examples of such sequences (1). This tetraloop is stabilized by an unusual set of H-bonds. G4 has syn conformation, and it forms a base pair with U1, which is very distinct from a classical GU wobble pair: iminoproton of G4 is H-bonded with carbonyl oxygen O2 of U1, and carbonyl oxygen O6 of G4 is H-bonded with the 2'-hydroxyl proton of U1; iminoproton of U1 is not involved in H-bonding. In addition, aminoproton of C3 forms an unusual H-bond with the phosphate oxygen OP2 of U2. Second residue, U2, is not involved in any base-specific interactions within the loop; all tetraloops of the UNCG family are expected to form similar structures. We have solved a high-resolution NMR structure of the UACG tetraloop and confirmed that its structure is very similar to the UUCG structure (2). Because the iminoproton of U1 is not involved in the H-bonding, it is expected that any pyrimidine can be accommodated in this position. Indeed, a high-resolution NMR structure of the CACG tetraloop solved recently in our lab (3) confirmed that it is very similar to both UUCG and UACG; a highly unusual feature of CACG is a stable non-Watson-Crick CG pair. Recent SELEX experiments showed that adenine residues can also be accommodated in the third loop position (4) Similar to C3 in the UUCG tetraloop, the adenine's aminogroup is situated on the major groove edge of the base, and it is potentially capable of forming an H-bond with the phosphate oxygen of the second residue. We will present results of molecular modeling for the UAAG loop (Figure), extending this family of tetraloops to YNMG (M = C or A, Y = C or U, N = any residue).

Nikolai B. Ulyanov1,*
Zhihua Du1
Jinghua Yu1
Luis R. Comolli1
William H. Gmeiner2
T. L. James1

1Mission Bay Genentech Hall
Department of Pharmaceutical Chemistry
University of California at San Francisco
San Francisco, CA 94143-2280
2Department of Biochemistry
Wake Forrest University School of Medicine
Winston-Salem, NC 27157-1016
*ulyanov@picasso.ucsf.edu

References and Footnotes
  1. Allain F. H. & Varani G. J. Mol. Biol. 250:333-53 (1995).
  2. Comolli L. R., Ulyanov N. B., Soto A. M., Marky L. A., James T. L. & Gmeiner W. H. Nucl. Acids Res. 30:4371-79 (2002).
  3. Du Z., Yu J., Andino R. & James T. L. Biochemistry, in press (2003).
  4. Proctor D. J., Schaak J. E., Bevilacqua J. M., Falzone C. J. & Bevilacqua P. C. Biochemistry 41:12062-75 (2002).