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Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity.

Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. Research Abstract Details 

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  • Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. Abstract Text:

    song caoSong Cao,shi-jie chenShi-Jie Chen,

    Using a combined master equation and kinetic cluster approach, we investigate RNA pseudoknot folding and unfolding kinetics. The energetic parameters are computed from a recently developed Vfold model for RNA secondary structure and pseudoknot folding thermodynamics. The folding kinetics theory is based on the complete conformational ensemble, including all the native-like and non-native states. The predicted folding and unfolding pathways, activation barriers, Arrhenius plots, and rate-limiting steps lead to several findings. First, for the PK5 pseudoknot, a misfolded 5' hairpin emerges as a stable kinetic trap in the folding process, and the detrapping from this misfolded state is the rate-limiting step for the overall folding process. The calculated rate constant and activation barrier agree well with the experimental data. Second, as an application of the model, we investigate the kinetic folding pathways for human telomerase RNA (hTR) pseudoknot. The predicted folding and unfolding pathways not only support the proposed role of conformational switch between hairpin and pseudoknot in hTR activity, but also reveal molecular mechanism for the conformational switch. Furthermore, for an experimentally studied hTR mutation, whose hairpin intermediate is destabilized, the model predicts a long-lived transient hairpin structure, and the switch between the transient hairpin intermediate and the native pseudoknot may be responsible for the observed hTR activity. Such finding would help resolve the apparent contradiction between the observed hTR activity and the absence of a stable hairpin.

    Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. Publishing Authors By Initials

    s caoS Cao,sj chenSJ Chen,

    For similar natural sciences: physics: thermodynamics research abstracts see: natural sciences: physics: thermodynamics research

    PUBMED ID PMID:

    MEDLINE DATE:

    Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Journal of molecular biology

    VOLUME: 367

    Page Numbers: 909-24

    Journal Abbreviation: J. Mol. Biol.

    ISSN: 0022-2836

    DAY: 9

    MONTH: 01

    YEAR: 2007

    Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985088

    Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. Keywords Mesh Terms:

    KEYWORDS: Thermodynamics

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity. Information

    Substance Name: Telomerase

    Registry Number: EC 2.7.7.49

    Grant and Affiliation Information for Biphasic folding kinetics of RNA pseudoknots and telomerase RNA activity.

    AFFILIATION: Department of Physics, University of Missouri-Columbia, Columbia, MO 65211, USA.

    Country: England

    England Research PublicationEngland Research Publication

    AGENCY: United States NIGMS

    GRANT: R01 GM063732-04

    ACRONYM: GM

    MEDLINETA: J Mol Biol

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

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