Thermodynamic Features of Structural Motifs Formed by β-L-RNA

Abstract

This is the first report to provide comprehensive thermodynamic and structural data concerning duplex, hairpin, quadruplex and i-motif structures in β-L-RNA series. Herein we confirm that, within the limits of experimental error, the thermodynamic stability of enantiomeric structural motifs is the same as that of naturally occurring D-RNA counterparts. In addition, formation of D-RNA/L-RNA heterochiral duplexes is also observed; however, their thermodynamic stability is significantly reduced in reference to homochiral D-RNA duplexes. The presence of three locked nucleic acid (LNA) residues within the D-RNA strand diminishes the negative effect of the enantiomeric, complementary L-RNA strand in the formation of heterochiral RNA duplexes. Similar behavior is also observed for heterochiral LNA-2′-O-methyl-D-RNA/L-RNA duplexes. The formation of heterochiral duplexes was confirmed by 1H NMR spectroscopy. The CD curves of homochiral L-RNA structural motifs are always reversed, whereas CD curves of heterochiral duplexes present individual features dependent on the composition of chiral strands.

RNA–DNA Chimeras in the Context of an RNA World Transition to an RNA/DNA World

“…[40,41] However,t he increased destabilization of duplexes above ac ertain threshold backbone heterogeneity may impede base-pair mediated higher order structure and function leading to "non-inheritable backbones". [44] All of these results,i ndicate that a) homogeneous backbones form duplexes that are stable and form catalysts that are functionally superior when compared to the heterogeneous backbone systems,and b) alimited amount of heterogeneous backbones could have played ar ole in the emergence of homogeneous systems [19,43] by selective pressures that would have been present to move the system from an initially heterogeneous backbone to ahomogeneous one. [18] Similar incorporation of 2'-5' linkages in RNAh as been shown to reduce or even abolish base-pairing [42] and also reduce aptamer activity [43] when compared to homogeneous parent systems.S uch heterogeneous backbone induced instability is also true for other systems such as backbones with mixed chirality.…”

“…[46][47][48] The thermally stable duplexes (composed of homogeneous and limited chimeric sequences) would persist, while the heterogeneous single strands hydrolyze back to their monomeric constituents to be recycled by the non-enzymatic oligomerization process to form oligomers of various compositions. [44,49] Instead of starting from ah omogeneous/chiral RNAworld, there could have been aheterogeneous/chiral mixture of RNAand DNA that could have led to the accumulation of the thermally and thermodynamically more stable homochiral homogeneous RNAa nd DNAs equences/duplexes/structures capable of fulfilling the informational and catalytic roles [50] necessary for Darwinian co-evolution (Scheme 2), avoiding the "prebiological necessity" for RNAt oi nvent catalysts to give rise to DNAand the subsequent genetic takeover. [11] Thec onsistent trends observed in the four sets of RNA/ DNAd uplex systems opens up the possibility that homogeneous backbone systems (RNAa nd DNA) may have been an atural outcome starting from ah eterogeneous prebiotic scenario, [14][15][16] as cenario that can be extended to the emergence of homochiral backbones as well.…”

Specific Binding of a d‐RNA G‐Quadruplex Structure with an l‐RNA Aptamer

“…Our proof‐of‐principle study here has demonstrated that an l ‐RNA aptamer can be used as a tool to recognize a d ‐rG4 of interest with strong affinity and specificity. l ‐RNAs were previously reported to be able to fold into a wide range of secondary structures, including G4, just like the natural d ‐RNAs . Also, structured l ‐RNA that can act on opposite‐handed RNAs with reactivity comparable to natural d ‐ribozymes were also reported .…”

RNA–DNA Chimeras in the Context of an RNA World Transition to an RNA/DNA World

“…Similar incorporation of 2′–5′ linkages in RNA has been shown to reduce or even abolish base‐pairing and also reduce aptamer activity when compared to homogeneous parent systems. Such heterogeneous backbone induced instability is also true for other systems such as backbones with mixed chirality . All of these results, indicate that a) homogeneous backbones form duplexes that are stable and form catalysts that are functionally superior when compared to the heterogeneous backbone systems, and b) a limited amount of heterogeneous backbones could have played a role in the emergence of homogeneous systems by selective pressures that would have been present to move the system from an initially heterogeneous backbone to a homogeneous one.…”

“…The consistent trends observed in the four sets of RNA/DNA duplex systems opens up the possibility that homogeneous backbone systems (RNA and DNA) may have been a natural outcome starting from a heterogeneous prebiotic scenario, a scenario that can be extended to the emergence of homochiral backbones as well . Instead of starting from a homogeneous/chiral RNA world, there could have been a heterogeneous/chiral mixture of RNA and DNA that could have led to the accumulation of the thermally and thermodynamically more stable homochiral homogeneous RNA and DNA sequences/duplexes/structures capable of fulfilling the informational and catalytic roles necessary for Darwinian co‐evolution (Scheme ), avoiding the “prebiological necessity” for RNA to invent catalysts to give rise to DNA and the subsequent genetic takeover .…”