Predicting the three-dimensional folding of transfer RNA with a computer modeling protocol

Hubbard, John M.; Hearst, John E.

doi:10.1021/bi00236a019

Cited by 21 publications

(6 citation statements)

References 23 publications

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“…One straightforward approach utilizes sets of connected double helical stems assembled to be consistent with distances and other experimentally determined constraints (14)(15)(16). Development of models from FRET studies of hammerhead RNAs is one example of such a constraint-based method (12).…”

Section: Introductionmentioning

confidence: 99%

A small modified hammerhead ribozyme and its conformational characteristics determined by mutagenesis and lattice calculation

Lustig¹,

Lin

Smith

et al. 1995

Nucl Acids Res

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A prototypic hammerhead ribozyme has three helices that surround an asymmetrical central core loop. We have mutagenized a hammerhead type ribozyme. In agreement with previous studies, progressive removal of stem-loop 11 from a three stemmed ribozyme showed that this region is not absolutely critical for catalysis. However, complete elimination of stem 11 and its loop did reduce, but did not eliminate, function. In a stem-loop Il-deleted ribozyme, activity was best preserved when a purine, prferably a G, was present at position 10

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Section: Introductionmentioning

confidence: 99%

A small modified hammerhead ribozyme and its conformational characteristics determined by mutagenesis and lattice calculation

Lustig¹,

Lin

Smith

et al. 1995

Nucl Acids Res

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“…The acceptor, T and anticodon helical stems are found to have near uniform helical character, while the D-stem shows considerable differences in both tRNA structures due to interactions with a third base. The sequence dependent local features characterized by our analysis can provide a more accurate input to the prediction algorithms for the three dimensional folding oftRNA molecules of known sequence (46). The fact that tRNA stems and A-form DNA oligonucleotides show nearly identical sequence dependent features indicates that these variations are typical characteristics for all A-type structures and are well determined even at the medium resolution x-ray data (2.5-3.0 A) obtained for the tRNA crystals.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Sequence Dependent Variations in Secondary and Tertiary Structure of tRNA Molecules

Bhattacharyya

Bansal

1994

Journal of Biomolecular Structure and Dynamics

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The double helical regions of the five tRNA(Phe) and two tRNA(Asp) crystal structures have been analyzed using the local basepair step parameters. The sequence dependent effects in the mini double helices of tRNA are very similar to those observed in the crystal structures of oligonucleotides in the A-form, the purine-pyrimidine and purine-purine steps have small roll angles when compared to the fiber models of A-DNA as well as A-RNA, while the pyrimidine-purine doublet steps have large roll angles. The orientation of the basepairs in the D-stem is unusual and invariant i.e. they are different from the other three stems but are very similar in all the five tRNA(Phe) crystal structures, presumably due to tertiary interaction of the Watson-Crick basepairs with other bases, with all bases being highly conserved. The origin of the differences between the tertiary structures of tRNA(Phe) and tRNA(Asp) from yeast has also been investigated. It is found that even though the angle between the acceptor arm and the D-stem is very similar in the two structures, the angle subtended by the acceptor arm and the anticodon arm is smaller in the tRNA(Phe) structure (by more than 10 degrees). This is due to differences in the orientation of the two mini helices constituting the anticodon arm, which are inclined to each other by approximately 25 degrees in tRNA(Phe) and 16 degrees in tRNA(Asp). In addition, the acceptor arm, the D-stem and the anticodon stem are nearly coplanar in tRNA(Phe), while in tRNA(Asp) the anticodon stem projects out of the plane defined by the acceptor arm and the anticodon stem. These two features together lead to a larger separation between the acceptor and anticodon ends in tRNA(Asp) and indicate that the junction between the D-stem and the anticodon stem is quite variable, with features characteristic of a ball-and-socket type joint and determined for each tRNA molecule by the base sequence at the junction.

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“…As seen with our ribosomal RNA fragment, compensatory base changes can suggest tertiary interactions, and computer studies show that relatively few such interactions need to be specified before the overall three-dimensional folding is strongly constrained. 33 Compensatory changes together with molecular modeling have already led to a surprisingly detailed proposal for the structure of the active site of the group I intron self-splicing RNA.34 Multidimensional NMR methods are currently being developed that will probably allow the complete proton spectra of modest-sized (540 nucleotide) RNAs to be assigned,35 and even in molecules the size of transfer RNA, techniques for extracting useful information from the imino proton region of the spectrum have been available for some time. 36 Thus there is every prospect that some aspects of our ribosomal RNA fragment structure will yield to NMR studies.…”

Section: Discussionmentioning

confidence: 99%

The RNA-folding problem

Draper¹

1992

Acc. Chem. Res.

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It is a central tenet of molecular biology that structure determines function, and indeed, spectacular insights into functions of specific proteins and DNA sequences have been based on structural studies of these molecules. The structures of a third class of biological macromolecules, RNAs, have not been studied nearly as intensively, with the consequence that details of their functions are poorly understood. This situation is changing as genetic and biochemical studies are bringing the in vivo roles of RNAs into sharper focus, and systematic methods for approaching RNA structure are developed.RNAs are intimately involved in the process of gene expression in cells, both as informational molecules and as part of the decoding machinery. By the early 1960s three kinds of RNAs had been discerned: messenger RNAs are DNA copies carrying the sequence specifying a gene; transfer RNAs are the "adaptors" which actually read the genetic code off the messenger and substitute the correct amino acid in the growing peptide chain; and the ribosome is an ~3-MDa (megadalton) complex of RNA and protein which facilitates the interaction of transfer and messenger RNAs while catalyzing peptide bond formation. Of these RNA classes, only the structure of transfer RNA is understood in any detail, based on single-crystal X-ray diffraction results1,2 and extensive physical studies of its folding.3 Messenger and ribosomal RNAs may reach thousands of nucleotides (in contrast to 75-80 nucleotides for transfer RNA); this has made determination of their structures a formidable experimental problem and is in part responsible for their neglect. The detailed structures of these larger RNAs probably were not seen as a pressing problem either: messengers were viewed as largely passive molecules, while ribosomal RNAs were thought to serve only as the scaffolding for the 50-80 proteins which were presumed to endow the ribosome with enzymatic properties.About a decade ago evidence started to accumulate in favor of active roles for messenger and ribosomal RNAs in gene expression. Direct involvement of ribosomal RNAs in several essential ribosome functions was discovered,4 while specific roles for ribosomal proteins remain elusive. In defiance of the classical formulation that gene expression is regulated by repressor proteins binding specific DNA sequences, many important regulatory pathways were found in which messenger RNA structures modulate translation and bind repressor (or activator) proteins.5 Finally, the discoveries of RNAs with catalytic activities provided convincing proof that David Draper, born In California In 1950, did his undergraduate work in biochemistry at the

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Predicting the three-dimensional folding of transfer RNA with a computer modeling protocol

Cited by 21 publications

References 23 publications

A small modified hammerhead ribozyme and its conformational characteristics determined by mutagenesis and lattice calculation

A small modified hammerhead ribozyme and its conformational characteristics determined by mutagenesis and lattice calculation

Analysis of Sequence Dependent Variations in Secondary and Tertiary Structure of tRNA Molecules

The RNA-folding problem

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