Cold denaturation of RNA secondary structures with loop entropy and quenched disorder

Iannelli, Flavio; Mamasakhlisov, Y. Sh.; Netz, Roland R.

doi:10.1103/physreve.101.012502

Cited by 4 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, numerical and theoretical studies of RNA-folding models have emphasized the importance of loop formation in the hybridization reaction ( 59 – 62 ). This might contribute to explaining a wide range of RNA behaviors, from misfolding ( 25 ) and multiplicity of native structures ( 63 ) to the RNA thermostatic and cold-denaturation phenomenon ( 64 , 65 ). Ultimately, the promiscuity of transiently stable RNA structures might be related to the diversity of physiological responses observed when such RNAs interact with the human genome, as in the case of the RNA viruses.…”

Section: Discussionmentioning

confidence: 99%

Stem–loop formation drives RNA folding in mechanical unzipping experiments

Rissone

Bizarro

Ritort

2022

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

View full text Add to dashboard Cite

Accurate knowledge of RNA hybridization is essential for understanding RNA structure and function. Here we mechanically unzip and rezip a 2-kbp RNA hairpin and derive the 10 nearest-neighbor base pair (NNBP) RNA free energies in sodium and magnesium with 0.1 kcal/mol precision using optical tweezers. Notably, force–distance curves (FDCs) exhibit strong irreversible effects with hysteresis and several intermediates, precluding the extraction of the NNBP energies with currently available methods. The combination of a suitable RNA synthesis with a tailored pulling protocol allowed us to obtain the fully reversible FDCs necessary to derive the NNBP energies. We demonstrate the equivalence of sodium and magnesium free-energy salt corrections at the level of individual NNBP. To characterize the irreversibility of the unzipping–rezipping process, we introduce a barrier energy landscape of the stem–loop structures forming along the complementary strands, which compete against the formation of the native hairpin. This landscape correlates with the hysteresis observed along the FDCs. RNA sequence analysis shows that base stacking and base pairing stabilize the stem–loops that kinetically trap the long-lived intermediates observed in the FDC. Stem–loops formation appears as a general mechanism to explain a wide range of behaviors observed in RNA folding.

show abstract

Section: Discussionmentioning

confidence: 99%

Stem–loop formation drives RNA folding in mechanical unzipping experiments

Rissone

Bizarro

Ritort

2022

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

View full text Add to dashboard Cite

show abstract

“…The increase in C p below T G (dashed grey band in Fig. 5B) is reminiscent of the glass transition predicted by statistical mod-9 els of RNA with quenched disorder (46,47). As C p = C U p C N p , we attribute this change to the sudden reduction in C N p and the configurational entropy loss upon forming N (25).…”

Section: Most Remarkable Is the Large C Cmentioning

confidence: 60%

Universal Cold RNA Phase Transitions

Rissone,

Severino,

Pastor

et al. 2024

Preprint

View full text Add to dashboard Cite

RNA's diversity of structures and functions impacts all life forms sinceprimordia. We use calorimetric force spectroscopy to investigate RNA folding landscapes in previously unexplored low-temperature conditions. We find that Watson-Crick RNA hairpins, the most basic secondary structure elements, undergo a glass-like transition below TG≈ 20 °C where the heat capacity abruptly changes and the RNA folds into a diversity of misfolded structures. We hypothesize that an altered RNA biochemistry, determined by sequence-independent ribose-water interactions, outweighs sequence-dependent base pairing. The ubiquitous ribose-water interactions lead to universal RNA phase transitions below TG, such as maximum stability at TS≈ 5 °C where water density is maximum, and cold denaturation at TC≈ -50 °C. RNA cold biochemistry may have a profound impact on RNA function and evolution.

show abstract

“…Indeed, numerical and theoretical studies of RNA folding models have emphasized the importance of loop formation in the hybridization reaction (59)(60)(61)(62). This might contribute to explain a wide range of RNA behaviors, from misfolding (25) and multiplicity of native structures (63), to the RNA thermostatic and cold-denaturation phenomenon (64,65). Ultimately, the promiscuity of transiently stable RNA structures might be related to the diversity of physiological responses observed when such RNAs interact with the human genome, as in the case of the RNA viruses.…”

Section: Discussionmentioning

confidence: 99%

Stem-loop formation drives RNA folding in mechanical unzipping experiments

Rissone,

Bizarro,

Ritort

2022

Preprint

View full text Add to dashboard Cite

Accurate knowledge of RNA hybridization is essential for understanding RNA structure and function. Here we mechanically unzip and rezip a 2kbp RNA hairpin and derive the ten nearest-neighbor base-pair (NNBP) RNA free energies in sodium and magnesium with 0.1 kcal/mol precision using optical tweezers. Notably, forcedistance curves (FDCs) exhibit strong irreversible effects with hysteresis and several intermediates, precluding the extraction of the NNBP energies with currently available methods. The combination of a suitable RNA synthesis with a tailored pulling protocol allowed us to obtain the fully reversible FDCs necessary to derive the NNBP energies. We demonstrate the equivalence of sodium and magnesium free-energy salt corrections at the level of individual NNBP. To characterize the irreversibility of the unzipping-rezipping process, we introduce a barrier energy landscape of the stem-loop structures forming along the complementary strands, which compete against the formation of the native hairpin. This landscape correlates with the hysteresis observed along the FDCs. RNA sequence analysis shows that base stacking and base-pairing stabilize the stem-loops that kinetically trap the long-lived intermediates observed in the FDC. Stemloops formation appears as a general mechanism to explain a wide range of behaviors observed in RNA folding.

show abstract

Cold denaturation of RNA secondary structures with loop entropy and quenched disorder

Cited by 4 publications

References 48 publications

Stem–loop formation drives RNA folding in mechanical unzipping experiments

Stem–loop formation drives RNA folding in mechanical unzipping experiments

Universal Cold RNA Phase Transitions

Stem-loop formation drives RNA folding in mechanical unzipping experiments

Contact Info

Product

Resources

About