Molecular Mechanism for Folding Cooperativity of Functional RNAs in Living Organisms

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

A diverse set of organisms has adapted to live under extreme conditions. The molecular origin of the stability is unclear, however. It is not known whether the adaptation of functional RNAs, which have intricate tertiary structures, arises from strengthening of tertiary or secondary structure. Herein we evaluate effects of sequence changes on the thermostability of tRNA phe using experimental and computational approaches. To separate out effects of secondary and tertiary structure on thermostability, we modify base pairing strength in the acceptor stem, which does not participate in tertiary structure. In dilute solution conditions, strengthening secondary structure leads to non-two-state thermal denaturation curves and has small effects on thermostability, or the temperature at which tertiary structure and function are lost. In contrast, under cellular conditions with crowding and Mg 2+ -chelated amino acids, where two-state cooperative unfolding is maintained, strengthening secondary structure enhances thermostability. Investigation of stabilities of each tRNA stem across 44 organisms with a range of optimal growing temperatures revealed that organisms that grow in warmer environments have more stable stems. We also used Shannon entropies to identify positions of higher and lower information content, or sequence conservation, in tRNA phe and found that secondary structures have modest information content allowing them to drive thermal adaptation, while tertiary structures have maximal information content hindering them from participating in thermal adaptation. Base-paired regions with no tertiary structure and modest information content thus offer a facile evolutionary route to enhancing the thermostability of functional RNA by the simple molecular rules of base pairing.

Original languageEnglish (US)
Pages (from-to)2994-3002
Number of pages9
JournalBiochemistry
Volume57
Issue number20
DOIs
StatePublished - May 22 2018

Fingerprint

RNA, Transfer, Phe
Base Pairing
RNA
Temperature
Entropy
Transfer RNA
Denaturation
Hot Temperature
Amino Acids
Conservation
Thermotolerance

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

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abstract = "A diverse set of organisms has adapted to live under extreme conditions. The molecular origin of the stability is unclear, however. It is not known whether the adaptation of functional RNAs, which have intricate tertiary structures, arises from strengthening of tertiary or secondary structure. Herein we evaluate effects of sequence changes on the thermostability of tRNA phe using experimental and computational approaches. To separate out effects of secondary and tertiary structure on thermostability, we modify base pairing strength in the acceptor stem, which does not participate in tertiary structure. In dilute solution conditions, strengthening secondary structure leads to non-two-state thermal denaturation curves and has small effects on thermostability, or the temperature at which tertiary structure and function are lost. In contrast, under cellular conditions with crowding and Mg 2+ -chelated amino acids, where two-state cooperative unfolding is maintained, strengthening secondary structure enhances thermostability. Investigation of stabilities of each tRNA stem across 44 organisms with a range of optimal growing temperatures revealed that organisms that grow in warmer environments have more stable stems. We also used Shannon entropies to identify positions of higher and lower information content, or sequence conservation, in tRNA phe and found that secondary structures have modest information content allowing them to drive thermal adaptation, while tertiary structures have maximal information content hindering them from participating in thermal adaptation. Base-paired regions with no tertiary structure and modest information content thus offer a facile evolutionary route to enhancing the thermostability of functional RNA by the simple molecular rules of base pairing.",
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Molecular Mechanism for Folding Cooperativity of Functional RNAs in Living Organisms. / Leamy, Kathleen A.; Yennawar, Neela; Bevilacqua, Philip C.

In: Biochemistry, Vol. 57, No. 20, 22.05.2018, p. 2994-3002.

Research output: Contribution to journalArticle

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