Towards structural genomics of RNA: Rapid NMR resonance assignment and simultaneous RNA tertiary structure determination using residual dipolar couplings Journal Article


Authors: Al-Hashimi, H. M.; Gorin, A.; Majumdar, A.; Gosser, Y.; Patel, D. J.
Article Title: Towards structural genomics of RNA: Rapid NMR resonance assignment and simultaneous RNA tertiary structure determination using residual dipolar couplings
Abstract: We report a new residual dipolar couplings (RDCs) based NMR procedure for rapidly determining RNA tertiary structure demonstrated on a uniformly 15N/13C-labeled 27 nt variant of the trans-activation response element (TAR) RNA from HIV-I. In this procedure, the time-consuming nuclear Overhauser enhancement (NOE)-based sequential assignment step is replaced by a fully automated RDC-based assignment strategy. This approach involves examination of all allowed sequence-specific resonance assignment permutations for best-fit agreement between measured RDCs and coordinates for sub-structures in a target RNA. Using idealized A-form geometries to model Watson-Crick helices and coordinates from a previous X-ray structure to model a hairpin loop in TAR, the best-fit RDC assignment solutions are determined very rapidly (<five minutes of computational time) and are in complete agreement with corresponding NOE-based assignments. Orientational constraints derived from RDCs are used simultaneously to assemble sub-structures into an RNA tertiary conformation. Through enhanced speeds of application and reduced reliance on chemical shift dispersion, this RDC-based approach lays the foundation for rapidly determining RNA conformations in a structural genomics context, and may increase the size limit of RNAs that can be examined by NMR. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: sequence analysis; mutation; rna; geometry; ribonomics; genomics; base sequence; hydrogen bonding; crystallography, x-ray; nucleic acid conformation; rna structure; sequence analysis, rna; dna responsive element; nuclear magnetic resonance; rna, viral; structural genomics; rna sequence; hiv-1; nuclear magnetic resonance, biomolecular; residual dipolar couplings; genome, viral; nuclear overhauser effect; rna conformation; hiv long terminal repeat; priority journal; article; hiv-i tar; resonance assignments
Journal Title: Journal of Molecular Biology
Volume: 318
Issue: 3
ISSN: 0022-2836
Publisher: Academic Press Inc., Elsevier Science  
Date Published: 2002-05-03
Start Page: 637
End Page: 649
Language: English
DOI: 10.1016/s0022-2836(02)00160-2
PUBMED: 12054812
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Yuying Gosser
    7 Gosser
  2. Dinshaw J Patel
    392 Patel