RNA G-quadruplexes emerge from a compacted coil-like ensemble via multiple pathways
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F25%3A00639192" target="_blank" >RIV/68081707:_____/25:00639192 - isvavai.cz</a>
Result on the web
<a href="https://academic.oup.com/nar/article/53/17/gkaf872/8249853" target="_blank" >https://academic.oup.com/nar/article/53/17/gkaf872/8249853</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkaf872" target="_blank" >10.1093/nar/gkaf872</a>
Alternative languages
Result language
angličtina
Original language name
RNA G-quadruplexes emerge from a compacted coil-like ensemble via multiple pathways
Original language description
RNA G-quadruplexes (rG4s) are emerging as vital structural elements involved in processes like gene regulation, translation, and genome stability. Found in untranslated regions of messenger RNAs (mRNAs), they influence translation efficiency and mRNA localization. Additionally, rG4s of long noncoding RNAs and telomeric RNA play roles in RNA processing and cellular aging. Despite their significance, the atomic-level folding mechanisms of rG4s remain poorly understood due to their complexity. We studied the folding of the r(GGGA)3GGG and r(GGGUUA)3GGG (TERRA) sequences into parallel-stranded rG4 using all-atom enhanced-sampling molecular dynamics simulations, applying well-tempered metadynamics coupled with solute tempering. The obtained folding pathways suggest that RNA initially adopts a compacted coil-like ensemble characterized by dynamic guanine stacking and pairing. The three-quartet rG4 gradually forms from this compacted coil ensemble via diverse routes involving strand rearrangements and guanine incorporations. While the folding mechanism is multipathway, various two-quartet rG4 structures appear to be a common transitory ensemble along most routes. Thus, the process seems more complex than previously predicted, as G-hairpins or G-triplexes do not act as distinct intermediates, even though some are occasionally sampled. We also discuss the challenges of applying enhanced sampling methodologies to such a multidimensional free-energy surface and address the force-field limitations.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/EF15_003%2F0000477" target="_blank" >EF15_003/0000477: Structural gymnastics of nucleic acids: from molecular principles through biological functions to therapeutic targets.</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nucleic Acids Research
ISSN
0305-1048
e-ISSN
1362-4962
Volume of the periodical
53
Issue of the periodical within the volume
17
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
gkaf872
UT code for WoS article
001566462300001
EID of the result in the Scopus database
2-s2.0-105015556322