Mapping the kinetic barriers of a Large RNA molecule's folding landscape.

The folding of linear polymers into discrete three-dimensional structures is often required for biological function. The formation of long-lived intermediates is a hallmark of the folding of large RNA molecules due to the ruggedness of their energy landscapes. The precise thermodynamic nature of the...

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Autores principales:	Jörg C Schlatterer, Joshua S Martin, Alain Laederach, Michael Brenowitz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1396c9de73b34f869f75aa23b2caea99
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spelling	oai:doaj.org-article:1396c9de73b34f869f75aa23b2caea992021-11-18T08:31:13ZMapping the kinetic barriers of a Large RNA molecule's folding landscape.1932-620310.1371/journal.pone.0085041https://doaj.org/article/1396c9de73b34f869f75aa23b2caea992014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586236/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The folding of linear polymers into discrete three-dimensional structures is often required for biological function. The formation of long-lived intermediates is a hallmark of the folding of large RNA molecules due to the ruggedness of their energy landscapes. The precise thermodynamic nature of the barriers (whether enthalpic or entropic) that leads to intermediate formation is still poorly characterized in large structured RNA molecules. A classic approach to analyzing kinetic barriers are temperature dependent studies analyzed with Eyring's transition state theory. We applied Eyring's theory to time-resolved hydroxyl radical (•OH) footprinting kinetics progress curves collected at eight temperature from 21.5 °C to 51 °C to characterize the thermodynamic nature of folding intermediate formation for the Mg(2+)-mediated folding of the Tetrahymena thermophila group I ribozyme. A common kinetic model configuration describes this RNA folding reaction over the entire temperature range studied consisting of primary (fast) transitions to misfolded intermediates followed by much slower secondary transitions, consistent with previous studies. Eyring analysis reveals that the primary transitions are moderate in magnitude and primarily enthalpic in nature. In contrast, the secondary transitions are daunting in magnitude and entropic in nature. The entropic character of the secondary transitions is consistent with structural rearrangement of the intermediate species to the final folded form. This segregation of kinetic control reveals distinctly different molecular mechanisms during the two stages of RNA folding and documents the importance of entropic barriers to defining rugged RNA folding landscapes.Jörg C SchlattererJoshua S MartinAlain LaederachMichael BrenowitzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e85041 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jörg C Schlatterer Joshua S Martin Alain Laederach Michael Brenowitz Mapping the kinetic barriers of a Large RNA molecule's folding landscape.
description	The folding of linear polymers into discrete three-dimensional structures is often required for biological function. The formation of long-lived intermediates is a hallmark of the folding of large RNA molecules due to the ruggedness of their energy landscapes. The precise thermodynamic nature of the barriers (whether enthalpic or entropic) that leads to intermediate formation is still poorly characterized in large structured RNA molecules. A classic approach to analyzing kinetic barriers are temperature dependent studies analyzed with Eyring's transition state theory. We applied Eyring's theory to time-resolved hydroxyl radical (•OH) footprinting kinetics progress curves collected at eight temperature from 21.5 °C to 51 °C to characterize the thermodynamic nature of folding intermediate formation for the Mg(2+)-mediated folding of the Tetrahymena thermophila group I ribozyme. A common kinetic model configuration describes this RNA folding reaction over the entire temperature range studied consisting of primary (fast) transitions to misfolded intermediates followed by much slower secondary transitions, consistent with previous studies. Eyring analysis reveals that the primary transitions are moderate in magnitude and primarily enthalpic in nature. In contrast, the secondary transitions are daunting in magnitude and entropic in nature. The entropic character of the secondary transitions is consistent with structural rearrangement of the intermediate species to the final folded form. This segregation of kinetic control reveals distinctly different molecular mechanisms during the two stages of RNA folding and documents the importance of entropic barriers to defining rugged RNA folding landscapes.
format	article
author	Jörg C Schlatterer Joshua S Martin Alain Laederach Michael Brenowitz
author_facet	Jörg C Schlatterer Joshua S Martin Alain Laederach Michael Brenowitz
author_sort	Jörg C Schlatterer
title	Mapping the kinetic barriers of a Large RNA molecule's folding landscape.
title_short	Mapping the kinetic barriers of a Large RNA molecule's folding landscape.
title_full	Mapping the kinetic barriers of a Large RNA molecule's folding landscape.
title_fullStr	Mapping the kinetic barriers of a Large RNA molecule's folding landscape.
title_full_unstemmed	Mapping the kinetic barriers of a Large RNA molecule's folding landscape.
title_sort	mapping the kinetic barriers of a large rna molecule's folding landscape.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/1396c9de73b34f869f75aa23b2caea99
work_keys_str_mv	AT jorgcschlatterer mappingthekineticbarriersofalargernamoleculesfoldinglandscape AT joshuasmartin mappingthekineticbarriersofalargernamoleculesfoldinglandscape AT alainlaederach mappingthekineticbarriersofalargernamoleculesfoldinglandscape AT michaelbrenowitz mappingthekineticbarriersofalargernamoleculesfoldinglandscape
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Mapping the kinetic barriers of a Large RNA molecule's folding landscape.

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