Folding of branched RNA species

Lilley, David M.J.

doi:10.1002/(sici)1097-0282(1998)48:2<101::aid-bip2>3.0.co;2-7

Cited by 36 publications

(29 citation statements)

References 109 publications

(94 reference statements)

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“…Although these base pairs are not directly involved in tertiary interactions in the crystal structure (Serganov et al 2004), they could be involved in the global architecture of the aptamer given their close proximity to the junction. Indeed, the global architecture of RNA junctions has been shown to be influenced by proximal base pairs by means of coaxial stacking (Lilley 1998). However, native gel and RNAse T1 assays performed on the aptamer variant C45G-G43C revealed that the looploop interaction can take place, suggesting that this mutation does not significantly perturb the loop-loop interaction (data not shown).…”

Section: Discussionmentioning

confidence: 97%

“…Therefore, we sought for evidences relating weak 2AP affinity and severe disruption of the loop-loop interaction by using a native gel electrophoresis assay. This technique can be used to study global conformational changes in nucleic acids whereby a compact structure generally migrates faster than a more extended one (Lilley 1998;Yamauchi et al 2005). We reasoned that aptamers having a functional loop-loop interaction should have a compact structure when compared to variants compromised in the interaction, and should therefore display a faster migration rate.…”

Section: Effect Of Position 15 On Ligand Bindingmentioning

confidence: 99%

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Core requirements of the adenine riboswitch aptamer for ligand binding

Lemay

Lafontaine²

2007

RNA

109

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The adenine riboswitch aptamer, the A box, positively regulates gene expression upon adenine binding. To provide insight into structure-function relationships, important for the adenine riboswitch aptamer, we have created alignments for six aptamer sequences that reveal the core requirements. In addition, 2-aminopurine (2AP) binding studies have been used to test the consensus sequence derived from the alignment. Overall, the consensus secondary structure is consistent with 2AP binding studies. However, a position in the core, previously identified as variable, shows restriction in nucleotide sequence. Furthermore, this restriction is found to be related with the ligand specificity of the riboswitch. The implications of this relationship for the riboswitch gene regulation mechanism are discussed.

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Section: Discussionmentioning

confidence: 97%

Section: Effect Of Position 15 On Ligand Bindingmentioning

confidence: 99%

Core requirements of the adenine riboswitch aptamer for ligand binding

Lemay

Lafontaine²

2007

RNA

109

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“…There are N linker (joining) sequences for N helices in a junction loop, although some of the linker sequences may be of zero length. Although junction loops have not been as systematically or extensively studied as the simpler hairpin and internal loops, some generalizations have been made for the more common three-way and four-way junctions (Lilley, 1998(Lilley, , 2000. Common examples of junction loops are those in tRNA and the hammerhead ribozyme.…”

Section: Junction Loops/multiloopsmentioning

confidence: 99%

RNA structural motifs: building blocks of a modular biomolecule

Hendrix

Brenner

Holbrook

2005

Quart. Rev. Biophys.

199

141

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Abstract. RNAs are modular biomolecules, composed largely of conserved structural subunits, or motifs. These structural motifs comprise the secondary structure of RNA and are knit together via tertiary interactions into a compact, functional, three-dimensional structure and are to be distinguished from motifs defined by sequence or function. A relatively small number of structural motifs are found repeatedly in RNA hairpin and internal loops, and are observed to be composed of a limited number of common 'structural elements '. In addition to secondary and tertiary structure motifs, there are functional motifs specific for certain biological roles and binding motifs that serve to complex metals or other ligands. Research is continuing into the identification and classification of RNA structural motifs and is being initiated to predict motifs from sequence, to trace their phylogenetic relationships and to use them as building blocks in RNA engineering.

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“…Like protein enzymes, they must fold into a conformation that provides a local environment in which catalysis can proceed. Branched helical junctions are very common in RNA and frequently are essential for their function (2), but the dynamic mechanisms by which the junctions contribute to RNA folding are not well understood.…”

mentioning

confidence: 99%

A four-way junction accelerates hairpin ribozyme folding via a discrete intermediate

Tan

Wilson

Nahas

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

194

230

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The natural form of the hairpin ribozyme comprises two major structural elements: a four-way RNA junction and two internal loops carried by adjacent arms of the junction. The ribozyme folds into its active conformation by an intimate association between the loops, and the efficiency of this process is greatly enhanced by the presence of the junction. We have used single-molecule spectroscopy to show that the natural form fluctuates among three distinct states: the folded state and two additional, rapidly interconverting states (proximal and distal) that are inherited from the junction. The proximal state juxtaposes the two loop elements, thereby increasing the probability of their interaction and thus accelerating folding by nearly three orders of magnitude and allowing the ribozyme to fold rapidly in physiological conditions. Therefore, the hairpin ribozyme exploits the dynamics of the junction to facilitate the formation of the active site from its other elements. Dynamic interplay between structural elements, as we demonstrate for the hairpin ribozyme, may be a general theme for other functional RNA molecules. R ibozymes, cellular RNA molecules that catalyze chemical reactions, have fundamental implications for the evolution of life on the planet and provide insight into biocatalysis in general (1). Like protein enzymes, they must fold into a conformation that provides a local environment in which catalysis can proceed. Branched helical junctions are very common in RNA and frequently are essential for their function (2), but the dynamic mechanisms by which the junctions contribute to RNA folding are not well understood.The hairpin ribozyme is one of the nucleolytic ribozymes that bring about a site-specific cleavage of the RNA backbone by means of a transesterification reaction in which the 2Ј oxygen attacks the 3Ј phosphorus, thereby breaking the bond to the 5Ј oxygen. The natural form of the hairpin ribozyme comprises two major structural elements: a four-way RNA junction and two internal loops carried by adjacent A and B arms of the junction (Fig. 1a). The loop-loop interaction is essential for the ribozyme activity, generating a 10 5 -fold acceleration of site-specific cleavage or ligation reactions. Although the minimal form without arms C and D can still catalyze the cleavage reaction and has yielded much insight into the catalytic mechanism (3), its folding requires two to three orders of magnitude higher Mg 2ϩ concentration (4-6), and the internal equilibrium between cleavage and ligation is shifted compared with the natural form (7).Ensemble fluorescence resonance energy transfer (FRET) studies have shown that the two loops are brought into close proximity at submillimolar Mg 2ϩ concentrations (4, 8), and extensive contacts between them have been identified from crystallographic analysis (9). The folded ribozyme has the neighboring helical arms coaxially stacked in pairs, A on D and B on C, with an antiparallel orientation of the continuous strands (Fig. 1b). The simple junction generated by replacin...

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Folding of branched RNA species

Cited by 36 publications

References 109 publications

Core requirements of the adenine riboswitch aptamer for ligand binding

Core requirements of the adenine riboswitch aptamer for ligand binding

RNA structural motifs: building blocks of a modular biomolecule

A four-way junction accelerates hairpin ribozyme folding via a discrete intermediate

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