Single base bulges in small RNA hairpins enhance ethidium binding and promote an allosteric transition

White, Su; Draper, David E.

doi:10.1093/nar/15.10.4049

Cited by 67 publications

(57 citation statements)

References 29 publications

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“…Finally, since the geometry of the bulged nucleotide is most probably an important feature of lariat formation, the intra-or extrahelical positioning of the bulged base has to be considered (34,42). The conformation of bulged nucleotides in RNA is not yet known, but by measuring ethidium bromide intercalation near bulged A, C, and U in an RNA helix, it was shown that all three bulged nucleotides have the same pronounced effect on the conformation of the sugar-phosphate backbone (60). Thus, the nucleotide conformations either are identical or differ by only a small free energy.…”

Section: Resultsmentioning

confidence: 99%

Unusual branch point selection in processing of human growth hormone pre-mRNA.

Hartmuth¹,

Barta²

1988

Mol. Cell. Biol.

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Intron A of the human growth hormone gene does not contain an A residue within 56 nucleotides preceding the 3' splice site. The analysis of the excised intron lariat revealed a C residue 28 nucleotides upstream fromn the 3' splice site as the major branch acceptor nucleotide. Two additional minor branched nucleotides were identified as U residues at positions -22 and -36. An adenosine substitution at position -22 results in lariat formation solely to this nucleotide. Therefore, C and U residues can function efficiently as natural branch acceptors, but an A residue is preferred if available in the proper region. In addition, the data strongly reinforce the importance of the distance constraint for lariat formation. To explain selection of the branch acceptor nucleotide, potential base-pairing interactions of branch point sequences with the U2 RNA are discussed.The excision of intervening sequences from nuclear premRNAs has been shown to occur via RNA lariat intermediates (for a review, see reference 39). Primary structural requirements for the formation of lariats in nuclear premRNAs involve sequences at the 5' splice site and the polypyrimidine stretch preceding the 3' splice site (1,15,46). In Saccharomyces cerevisiae, the invariant UACUAAC sequence 20 to 60 nucleotides upstream from the 3' end of the intron was found to be necessary for lariat formation, whereby the third adenosine nucleotide functions as the branch acceptor (12,29,48). The search for a similar sequence in higher eucaryotic pre-mRNAs resulted initially in the proposal of a fairly degenerated consensus sequence (26). From further analyses of branch points of a number of naturally occurring genes and of genes with mutant introns, it became clear that no strict consensus sequence surrounding the branched nucleotide could be defined (40,46,50). However, the adenosine as branch acceptor nucleotide appeared to be conserved. Recently, an adenosine residue was also identified as the branch acceptor in group II introns (53, 57). In addition, there seemed to be a distance constraint for the branch acceptor, which for higher eucaryotic premRNAs was always found within 18 to 40 nucleotides upstream from the 3' splice site (40,46,50).Selection of the branch point poses the problem of positioning the branch acceptor such that its 2' OH group is in a sterically favorable position to attack the phosphodiester bond adjacent to the 5' splice site. Recently, group II introns have been shown to be excised as lariats, and at least some of them are capable of self-splicing in vitro (44,53,57). This implies that the functions required for precise splicing are provided in cis and correlates well with a defined RNA secondary structure in group II introns (23, 33, 52). Moreover, similarities in the splicing mechanisms as well as in the intron boundaries suggest that nuclear and group II introns are evolutionarily related (7). However, the excision of nuclear introns is strongly dependent on trans-acting factors such as small nuclear ribonucleoproteins (snRNPs) and prot...

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Section: Resultsmentioning

confidence: 99%

Unusual branch point selection in processing of human growth hormone pre-mRNA.

Hartmuth¹,

Barta²

1988

Mol. Cell. Biol.

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“…Bulged nucleotides have been shown to be important structural motifs in various RNAs (Wu and Uhlenbeck, 1987;White and Draper, 1987). In most cases, a C is present at residue 3 17 in severe to lethal PSTVd strains, whereas a U is present at this position in mild to intermediate strains (Schnolzer et a/., 1985;Zimmat et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the virulence modulating region of potato spindle tuber viroid (PSTVd) by site-directed mutagenesis

Hammond¹

1992

Virology

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A series of nucleotide substitutions (G,, --f C; Cd7 + A; C,,, + U; U3,7 + C) were introduced into the virulence modulating region of the intermediate strain of potato spindle tuber viroid (PSTVd) in order to examine their effect upon viroid infectivity and pathogenicity with the presence of all four mutations resulting in the sequence of a previously reported severe strain of PSTVd. Eight of the resulting mutant cDNAs were characterized for infectivity and symptom induction in tomato, and the secondary structure of their corresponding RNAs was examined. The combined results of infectivity, computer analysis, and chemical mapping data imply that a previously proposed correlation between thermodynamic stability and PSWd pathogenicity does not hold true in all cases and suggest that conformation and/or sequence-specific interactions with host factors play a role in symptom development.o 1992 Academic PES, I~c.

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“…HIV-1 RRE <1 µM [176] 46 Delfinidin tRNA 10 µM [177] 47 Dichlorolissoclimide Inhibit eukaryotic protein synthesis 0.7 µM inhibition of protein synthesis only reported [166] 48 Doxycycline Small subunit fivefold tighter than tetracycline [167] 49 Erythromycin PTC 0.99 µM 1yi2 [178] 50 Ethidium bromide RNA/DNA heteroduplex, bulged RNA 3.3 µM [179,180] [189,190] 58 Hypoxanthine Guanine riboswitch 50 nM 2ees…”

Section: Db340mentioning

confidence: 99%

Strategies for the Design of Rna-Binding Small Molecules

Aboul‐ela

2009

Future Med. Chem.

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Bacterial ribosomal RNA is the target of clinically important antibiotics, while biologically important RNAs in viral and eukaryotic genomes present a range of potential drug targets. The physicochemical properties of RNA present difficulties for medicinal chemistry, particularly when oral availability is needed. Peptidic ligands and analysis of their RNA-binding properties are providing insight into RNA recognition. RNA-binding ligands include far more chemical classes than just aminoglycosides. Chemical functionalities from known RNA-binding small molecules are being exploited in fragment- and ligand-based projects. While targeting of RNA for drug design is very challenging, continuing advances in our understanding of the principles of RNA-ligand interaction will be necessary to realize the full potential of this class of targets.

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Single base bulges in small RNA hairpins enhance ethidium binding and promote an allosteric transition

Cited by 67 publications

References 29 publications

Unusual branch point selection in processing of human growth hormone pre-mRNA.

Unusual branch point selection in processing of human growth hormone pre-mRNA.

Analysis of the virulence modulating region of potato spindle tuber viroid (PSTVd) by site-directed mutagenesis

Strategies for the Design of Rna-Binding Small Molecules

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