The Trouble with Long-Range Base Pairs in RNA Folding

Author(s):  
Fabian Amman ◽  
Stephan H. Bernhart ◽  
Gero Doose ◽  
Ivo L. Hofacker ◽  
Jing Qin ◽  
...  
Keyword(s):  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Svetlana Kalmykova ◽  
Marina Kalinina ◽  
Stepan Denisov ◽  
Alexey Mironov ◽  
Dmitry Skvortsov ◽  
...  

AbstractThe ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. Current knowledge on functional RNA structures is focused on locally-occurring base pairs. However, crosslinking and proximity ligation experiments demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved complementary regions (PCCRs) in human protein-coding genes. PCCRs tend to occur within introns, suppress intervening exons, and obstruct cryptic and inactive splice sites. Double-stranded structure of PCCRs is supported by decreased icSHAPE nucleotide accessibility, high abundance of RNA editing sites, and frequent occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNAPII slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. The enrichment of 3’-ends within PCCRs raises the intriguing hypothesis that coupling between RNA folding and splicing could mediate co-transcriptional suppression of premature pre-mRNA cleavage and polyadenylation.


2020 ◽  
Author(s):  
Zhongwei Li ◽  
Keli Han

Base-stacked structure is an important feature of DNA molecules. Previous studies on the stacking effect concerning DNA-mediated hole transfer have revealed the influence of neighboring bases on onsite energies. But the neighboring base effect acts only in a short-distance. Besides it, a long-range (longer than three base pairs) stacking effect called squeezing effect in this paper has not yet been reported. Such a squeezing effect causes the bases near the middle of a sequence consisting of same type base pairs have lower onsite energies than the bases near the terminals. We predict it by H ̈uckelanalysis in an unconventional way and confirmed it by semiempirical calculations combinated with molecular dynamics simulations. The results suggest that in order to obtain a reasonable onsite energy map when study charge transfer on DNA, the stacking effects should be considered in a long-distance as possible. The consideration of squeezing effect also provides a new suggestion on the driving force of fluctuation-assisted DNA charge transfer. The method used to calculate the onsite energies in abase stack can be generalized to other π-stacked systems.<br><br>


2002 ◽  
Vol 01 (01) ◽  
pp. 225-244 ◽  
Author(s):  
YI JING YAN ◽  
HOUYU ZHANG

This article reviews our recent theoretical development toward understanding the interplay of electronic structure and dephasing effects on charge transfer/transport through molecular donor-bridge-acceptor systems. Both the generalized scattering matrix and Green's function formalisms for partially incoherent tunneling processes are summarized. Presented is also an exact mapping between the kinetic rate constants and the electric conductances in evaluation of chemical yields of sequential charge transfer in the presence of competing branching reactions. As an important example, the mechanism of long-range charge transfer in DNA in aqueous solution is investigated with a quantum chemistry implementation of the generalized Green's function formalism. A time scale of about 5 ps is found for the partially incoherent tunneling through a thymine/adenine π-stack in DNA. Numerical results further show that while the carrier oxidative charge does hop sequentially over all guanine sites in a DNA duplex, its tunneling over thymine/adenine bridge base pairs deviates substantially from the superexchange regime. Presented are also evidences for the involvement of both intrastrand and interstrand pathways in the ground state hole charge transfer in DNA.


ChemPhysChem ◽  
2015 ◽  
Vol 16 (8) ◽  
pp. 1607-1612 ◽  
Author(s):  
Effi Bätzner ◽  
Yu Liang ◽  
Caroline Schweigert ◽  
Andreas-Neil Unterreiner ◽  
Hans-Achim Wagenknecht

Fractals ◽  
1995 ◽  
Vol 03 (02) ◽  
pp. 269-284 ◽  
Author(s):  
S. HAVLIN ◽  
S.V. BULDYREV ◽  
A.L. GOLDBERGER ◽  
R.N. MANTEGNA ◽  
C.-K. PENG ◽  
...  

We present evidence supporting the idea that the DNA sequence in genes containing noncoding regions is correlated, and that the correlation is remarkably long range—indeed, base pairs thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the “non-stationarity” feature of the sequence of base pairs by applying a new algorithm called Detrended Fluctuation Analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and noncoding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to all eukaryotic DNA sequences (33 301 coding and 29 453 noncoding) in the entire GenBank database. We describe a simple model to account for the presence of long-range power-law correlations which is based upon a generalization of the classic Lévy walk. Finally, we describe briefly some recent work showing that the noncoding sequences have certain statistical features in common with natural languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts, and the Shannon approach to quantifying the “redundancy” of a linguistic text in terms of a measurable entropy function. We suggest that noncoding regions in plants and invertebrates may display a smaller entropy and larger redundancy than coding regions, further supporting the possibility that noncoding regions of DNA may carry biological information.


2020 ◽  
Author(s):  
Jeffrey E. Ehrhardt ◽  
Kevin M. Weeks

AbstractMethods for capturing the folding dynamics of functionally important RNAs, especially large RNAs, have relied primarily on global measurements of structure or on per-nucleotide chemical probing. These approaches infer, but do not directly measure, through-space tertiary interactions. Here we introduce trimethyloxonium (TMO) as a chemical probe for RNA. TMO enables time-resolved, single-molecule, through-space structure probing of RNA folding using a correlated chemical probing framework. TMO methylates RNA about 90 times faster than the widely used dimethyl sulfate probe, allowing structure interrogation on the second time scale. We used TMO to monitor folding of the RNase P RNA – a functional RNA with extensive long-range and noncanonical interactions – by direct measurement of through-space tertiary interactions in a time-resolved way. Time-dependent correlation changes directly revealed the central role of a long-range tertiary loop-loop interaction that guides native RNA folding. Single-molecule, time-resolved RNA structure probing with TMO is poised to reveal a wide range of dynamic RNA folding processes and principles of RNA folding.


2021 ◽  
Author(s):  
Rajeev Yadav ◽  
Julia Widom ◽  
Adrien Chauvier ◽  
Nils Walter

Abstract The archetypical transcriptional crcB fluoride riboswitch from Bacillus cereus is an intricately structured non-coding RNA element enhancing gene expression in response to toxic levels of fluoride. Here, we used single molecule FRET to uncover three dynamically interconverting conformations appearing along the transcription process: two distinct undocked states and one pseudoknotted docked state. We find that the fluoride anion specifically snap-locks the magnesium-induced, dynamically docked state. The long-range, nesting, single base pair A40-U48 acts as the main linchpin, rather than the multiple base pairs comprising the pseudoknot. We observe that the proximally paused RNA polymerase further fine-tunes the free energy to promote riboswitch docking. Finally, we show that fluoride binding at short transcript lengths is an early step toward partitioning folding into the docked conformation. These results reveal how the anionic fluoride ion cooperates with the magnesium-associated RNA to govern regulation of downstream genes needed for fluoride detoxification of the cell.


2010 ◽  
Vol 38 (2) ◽  
pp. 404-409 ◽  
Author(s):  
Mark D. Szczelkun ◽  
Peter Friedhoff ◽  
Ralf Seidel

Many biological processes rely on the interaction of proteins with multiple DNA sites separated by thousands of base pairs. These long-range communication events can be driven by both the thermal motions of proteins and DNA, and directional protein motions that are rectified by ATP hydrolysis. The present review describes conflicting experiments that have sought to explain how the ATP-dependent Type III restriction–modification enzymes can cut DNA with two sites in an inverted repeat, but not DNA with two sites in direct repeat. We suggest that an ATPase activity may not automatically indicate a DNA translocase, but can alternatively indicate a molecular switch that triggers communication by thermally driven DNA sliding. The generality of this mechanism to other ATP-dependent communication processes such as mismatch repair is also discussed.


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