Research article summary (published 3 Oct 2009):

Assembly mechanisms of RNA pseudoknots are determined by the stabilities of constituent secondary structures.

Full Abstract

Understanding how RNA molecules navigate their rugged folding landscapes holds the key to describing their roles in a variety of cellular functions. To dissect RNA folding at the molecular level, we performed simulations of three pseudoknots (MMTV and SRV-1 from viral genomes and the hTR pseudoknot from human telomerase) using coarse-grained models. The melting temperatures from the specific heat profiles are in good agreement with the available experimental data for MMTV and hTR. The equilibrium free energy profiles, which predict the structural transitions that occur at each melting temperature, are used to propose that the relative stabilities of the isolated helices control their folding mechanisms. Kinetic simulations, which corroborate the inferences drawn from the free energy profiles, show that MMTV folds by a hierarchical mechanism with parallel paths, i.e., formation of one of the helices nucleates the assembly of the rest of the structure. The SRV-1 pseudoknot, which folds in a highly cooperative manner, assembles in a single step in which the preformed helices coalesce nearly simultaneously to form the tertiary structure. Folding occurs by multiple pathways in the hTR pseudoknot, the isolated structural elements of which have similar stabilities. In one of the paths, tertiary interactions are established before the formation of the secondary structures. Our work shows that there are significant sequence-dependent variations in the folding landscapes of RNA molecules with similar fold. We also establish that assembly mechanisms can be predicted using the stabilities of the isolated secondary structures.

Author information

Author/s: Cho, Samuel S (SS); Pincus, David L (DL); Thirumalai, D (D);

Affiliation: Biophysics Program, Institute for Physical Science and Technology, and Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2009-Oct; vol 106 (issue 41) : pp 17349-54

Dates: Created 2009/10/15; Completed 2009/11/03; Revised 2009/11/06;

PMID: 19805055, status: MEDLINE (last retrieval date: 11/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Cell Line, Tumor Computer Simulation Genome, Viral Hot Temperature Humans Kinetics Mammary Tumor Virus, Mouse - chemistry; enzymology; genetics Mason-Pfizer monkey virus - chemistry; enzymology; genetics

Models, Molecular Molecular Conformation Nucleic Acid Conformation Nucleic Acid Denaturation RNA - chemistry RNA, Viral - chemistry; metabolism Telomerase - metabolism Thermodynamics

Associated Chemicals: RNA, Viral (0) ; RNA (63231-63-0) ; Telomerase (EC 2.7.7.49)

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