Progression of a loop-loop complex to a four-way junction is crucial for the activity of a regulatory antisense RNA

Kolb, Fabrice A.; Engdahl, Hilde M.; Slagter-Jäger, Jacoba G.; Ehresmann, Bernard; Ehresmann, Chantal; Westhof, Éric; Wagner, E. Gerhart H.; Romby, Pascale

doi:10.1093/emboj/19.21.5905

Cited by 98 publications

(78 citation statements)

References 44 publications

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“…This progression is dependent on the presence of bulges in the hairpin stems 60 that presumably aid the transformation by destabilizing the stems. Intriguingly, the number of base pairs in the two intermolecular helices is thought to be 15 with six bases in each of the loops connecting the ends of these helices, 58,59 which is extremely similar to the detailed structure of our kissing complexes.…”

Section: A Topologically Unlinked Complex; Lk =mentioning

confidence: 69%

“…Furthermore, a structure very similar to that reported here has also been identified for an "extended" kissing complex between messenger and antisense RNA that also involves parallel helices and a four-way junction. [58][59][60] As with any study with a coarse-grained model, one needs to consider how robust the results are and whether they might reflect any weaknesses of the model. We explicitly checked this for the repulsion between backbone sites in Section III D and found that although the results could change significantly when varying this parameter, our current value appears to be physically most reasonable.…”

Section: Discussionmentioning

confidence: 99%

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The effect of topology on the structure and free energy landscape of DNA kissing complexes

Romano

Hudson

Doye

et al. 2012

The Journal of Chemical Physics

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We use a recently developed coarse-grained model for DNA to study kissing complexes formed by hybridization of complementary hairpin loops. The binding of the loops is topologically constrained because their linking number must remain constant. By studying systems with linking numbers −1, 0, or 1 we show that the average number of interstrand base pairs is larger when the topology is more favourable for the right-handed wrapping of strands around each other. The thermodynamic stability of the kissing complex also decreases when the linking number changes from −1 to 0 to 1. The structures of the kissing complexes typically involve two intermolecular helices that coaxially stack with the hairpin stems at a parallel four-way junction.

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Section: A Topologically Unlinked Complex; Lk =mentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

The effect of topology on the structure and free energy landscape of DNA kissing complexes

Romano

Hudson

Doye

et al. 2012

The Journal of Chemical Physics

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“…In the case of the dimer initiation complex of the HIV-genomic RNA, a metastable intermolecular kissing interaction culminates in a linear duplex isoform stabilized by intermolecular base pairing (20,44). A kissing interaction also initiates the binding of the antisense RNA CopA to its target, CopT, but the outcome of this interaction is an unusual four-way junction defined by the predicted base stacking arrangements of intramolecular helices and newly formed intermolecular helices (19,45). In these types of kissing complexes, the intramolecular helices contributing to the initial kissing complex are replaced with intermolecular helices within an extended complex.…”

Section: Discussionmentioning

confidence: 99%

Intramolecular secondary structure rearrangement by the kissing interaction of the Neurospora VS ribozyme

Andersen

Collins

2001

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

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Kissing interactions in RNA are formed when bases between two hairpin loops pair. Intra-and intermolecular kissing interactions are important in forming the tertiary or quaternary structure of many RNAs. Self-cleavage of the wild-type Varkud satellite (VS) ribozyme requires a kissing interaction between the hairpin loops of stemloops I and V. In addition, self-cleavage requires a rearrangement of several base pairs at the base of stem I. We show that the kissing interaction is necessary for the secondary structure rearrangement of wild-type stem-loop I. Surprisingly, isolated stem-loop V in the absence of the rest of the ribozyme is sufficient to rearrange the secondary structure of isolated stem-loop I. In contrast to kissing interactions in other RNAs that are either confined to the loops or culminate in an extended intermolecular duplex, the VS kissing interaction causes changes in intramolecular base pairs within the target stem-loop.R NA kissing interactions, also called loop-loop pseudoknots, occur when the unpaired nucleotides in one hairpin loop base pair with the unpaired nucleotides in another hairpin loop (1). When the hairpin loops are located on separate RNA molecules, their intermolecular interaction is called a kissing complex. These interactions generally form between stem-loops containing extensive complementarity; however, stable complexes have been observed containing only two intermolecular Watson-Crick base pairs (2).Intramolecular kissing interactions are observed in the native structures of a variety of RNAs including Varkud satellite (VS) RNA, tRNA, and group I introns (3-6). These kissing interactions contribute to the assembly and stabilization of their respective RNA structures by joining and orienting helices. Kissing interactions may stabilize both native and nonnative interactions during tertiary folding, which can affect the rate at which the native structure is formed (7). Kissing interactions often form distorted structures that can serve as recognition sites for proteins, RNAs, metal ions, or other ligands (8-10). As a result, kissing interactions contribute to the stability of an RNA structure by affecting both global and local RNA interactions.The transient formation of an intermolecular kissing complex is required for RNA dimerization during the life cycle of retroviruses (11-15), and for the formation of some antisensetarget complexes (16,17). Kissing complexes in which the loop nucleotides are complementary can form stable dimers that contain intermolecular base pairs between the loop nucleotides only. Other stem-loops with more extensive complementarity sometimes form unstable kissing complexes, which are quickly remodeled into stable duplex or cruciform isoforms (18)(19)(20). Secondary structure remodeling involves breaking intramolecular base pairs in each hairpin and using the bases to form intermolecular helices.The VS ribozyme contains a kissing interaction that is required for self-cleavage of the wild-type RNA in vitro (6). This interaction involves Watson-Crick bas...

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“…These riboregulators are transcribed in response to various changes in the environment, and can in turn regulate genes by base pairing with target mRNAs in the regions overlapping or adjacent to the RBS. The sRNA-mRNA interactions can occur within a single region, as for the replication control of plasmid R1 by CopA RNA 32 and the control of biosynthesis of the RNA polymerase σ s -factor by DsrA RNA 33,34 , or within two regions that are distant or close to each other, as for DsrA-and OxyS-mediated control of transcription factor production 33,35,36 (FIG. 3b-c).…”

Section: Rna Controls Rnamentioning

confidence: 99%

Ribozymes, riboswitches and beyond: regulation of gene expression without proteins

2007

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Although various functions of RNA are carried out in conjunction with proteins, some catalytic RNAs, or ribozymes, which contribute to a range of cellular processes, require little or no assistance from proteins. Furthermore, the discovery of metabolite-sensing riboswitches and other types of RNA sensors has revealed RNA-based mechanisms that cells use to regulate gene expression in response to internal and external changes. Structural studies have shown how these RNAs can carry out a range of functions. In addition, the contribution of ribozymes and riboswitches to gene expression is being revealed as far more widespread than was previously appreciated. These findings have implications for understanding how cellular functions might have evolved from RNA-based origins.More than 40 years of extensive research has revealed that RNAs participate in a range of cellular functions. Some RNAs, despite being composed of only four chemically similar nucleotides, can fold into distinct three-dimensional architectures. In many cases, these constitute simple scaffolds that provide binding sites for proteins that function together with the RNAs. However, the discovery of the first catalytic RNAs -later named RNA enzymes, or ribozymes -in the 1980s demonstrated that RNAs can also have important functional roles in their own right 1,2 . The list of naturally occuring ribozymes is short, and additions over the years have been rare, with each new discovery eliciting considerable excitement in the field.Studies of molecular evolution suggest that RNA molecules significantly influenced the development of modern organisms by mediating the genetic flow from DNA to proteins, as well as through their own contribution to catalytic functions. The 'RNA world' hypothesis implies that RNA molecules appeared before DNA and proteins 3 . Nevertheless, even with a head start, RNA catalysts do not prevail in the modern world. Moreover, most ubiquitous ribozymes require proteins for efficient catalysis in vivo, and most true protein-devoid catalytic RNAs have been found in only a few viral-like sources, suggesting that the contribution of protein-free RNAs to the functions of modern cells has been limited.Correspondence to A.S. or D.J.P. serganoa@mskcc.org; pateld@mskcc.org. Competing interests statementThe authors declare no competing financial interests. HHS Public AccessAuthor manuscript Nat Rev Genet. Author manuscript; available in PMC 2015 December 23. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe discovery of riboswitches 4-6 and other RNA-based sensors reignited interest in the roles of protein-devoid RNA-based elements. These RNA sensors can be broadly defined as mRNA regions that are capable of modulating gene expression in response to internal and external inputs, without the initial participation of proteins. Unlike ribozymes, many of these sensors direct gene expression purely through changes in RNA conformation. For instance, riboswitches alter their conformations in response to small metabolite...

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Progression of a loop-loop complex to a four-way junction is crucial for the activity of a regulatory antisense RNA

Cited by 98 publications

References 44 publications

The effect of topology on the structure and free energy landscape of DNA kissing complexes

The effect of topology on the structure and free energy landscape of DNA kissing complexes

Intramolecular secondary structure rearrangement by the kissing interaction of the Neurospora VS ribozyme

Ribozymes, riboswitches and beyond: regulation of gene expression without proteins

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