Higher order structure in ribosomal RNA.

Gutell, Robin R.; Noller, Harry F.; Woese, Carl R.

doi:10.1002/j.1460-2075.1986.tb04330.x

Cited by 102 publications

(53 citation statements)

References 13 publications

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“…Mutual information indicates the extent to which the nucleotide identity at one position in a sequence alignment provides information about the nucleotide at a second position (Chiu and Kolodziejczak 1991;Gutell et al 1992) and has been previously used to identify correlated positions in both functional RNAs (Gutell et al 1986(Gutell et al , 1992Chiu and Kolodziejczak 1991;Gautheret et al 1995;Brown et al 1996) and proteins (Martin et al 2005). To assess the significance of these mutual information values, 1000 control alignments were generated in which the order of nucleotides in each variable column of the ribozyme alignment was randomly shuffled while preserving nucleotide composition.…”

Section: Identification Of Correlated Pairs Of Positions Using Mutualmentioning

confidence: 99%

Synthetic shuffling and in vitro selection reveal the rugged adaptive fitness landscape of a kinase ribozyme

Curtis

Bartel

2013

RNA

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The relationship between genotype and phenotype is often described as an adaptive fitness landscape. In this study, we used a combination of recombination, in vitro selection, and comparative sequence analysis to characterize the fitness landscape of a previously isolated kinase ribozyme. Point mutations present in improved variants of this ribozyme were recombined in vitro in more than 10 14 different arrangements using synthetic shuffling, and active variants were isolated by in vitro selection. Mutual information analysis of 65 recombinant ribozymes isolated in the selection revealed a rugged fitness landscape in which approximately one-third of the 91 pairs of positions analyzed showed evidence of correlation. Pairs of correlated positions overlapped to form densely connected networks, and groups of maximally connected nucleotides occurred significantly more often in these networks than they did in randomized control networks with the same number of links. The activity of the most efficient recombinant ribozyme isolated from the synthetically shuffled pool was 30-fold greater than that of any of the ribozymes used to build it, which indicates that synthetic shuffling can be a rich source of ribozyme variants with improved properties.

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Section: Identification Of Correlated Pairs Of Positions Using Mutualmentioning

confidence: 99%

Synthetic shuffling and in vitro selection reveal the rugged adaptive fitness landscape of a kinase ribozyme

Curtis

Bartel

2013

RNA

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“…The exceptionally strong comparative support for the 570:866 pseudoknot base pair is shown with the frequencies in Figure 9B. 20 Other base pairs in Figure 8A Figure 8 and nearly all of the other refinements in the 16S and 23S rRNA (see below).…”

Section: Lesson Seven-finalizing the Comparative Structure Model And mentioning

confidence: 86%

“…The analysis with the number pattern facilitated the identification of the first tertiary interaction in the 16S rRNA between position 570 and 866 in 1986. 20 This covariation method also enabled the identification of more pseudoknotted tertiary structure base pairs and non-canonical base pairs in the rRNAs.…”

Section: Covariation Methods-number Patternmentioning

confidence: 99%

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Ten lessons with Carl Woese about RNA and comparative analysis

Gutell

2014

RNA Biology

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For the Escherichia coli 16S rRNA, a molecule with 1542 nucleotides, 1,2 and the focus of our initial attention, the number of potential helices with a minimum of four base pairs is approximately 15 000 (Fig. 1, below diagonal) while 100 of these are in the correct comparative structure model ( Fig. 1, in red above diagonal). The actual percentage of correct helices divided by all possible helices is even smaller than this ~100/15 000 ratio. Of the ~100 helices in the correct comparative secondary structure, nearly 50% of them contain only two or three base pairs. Thus, the set of all possible helices should include all helices with at least two (not four) base pairs. The number of possible helices for E.coli 16S rRNA is ~100 000 (not ~15 000). The C/P ratio, where C = number of correct helices and P = all possible helices, is a useful metric to gauge one aspect of the complexity of RNA folding. And for E.coli 16S rRNA, the arithmetic is simple. Approximately one helix in every 1000 potential helices is correct. C/P = 1/1000.

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“…These searches have not been confined to canonical pairing rules or even pairwise interactions: any sequence change that is always accompanied by specific changes in one or more other bases will be detected (5). A number of potential interactions have been detected in this way, and some suggest unusual structures containing pseudoknots or noncanonical pairings (6)(7)(8).…”

mentioning

confidence: 99%