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Thermodynamic and Structural Studies...

Berger, Kyle D.

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Thermodynamic and Structural Studies of RNA Internal Loops Closed by GU Pairs.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Thermodynamic and Structural Studies of RNA Internal Loops Closed by GU Pairs./
Author:	Berger, Kyle D.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	185 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-10, Section: B.
Contained By:	Dissertations Abstracts International80-10B.
Subject:	Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13426779
ISBN:	9781392007044

Thermodynamic and Structural Studies of RNA Internal Loops Closed by GU Pairs.
Berger, Kyle D.

Thermodynamic and Structural Studies of RNA Internal Loops Closed by GU Pairs. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 185 p.

Source: Dissertations Abstracts International, Volume: 80-10, Section: B.

Thesis (Ph.D.)--University of Rochester, 2019.

This item is not available from ProQuest Dissertations & Theses.

The structure of RNA is largely dictated by its base to base interactions. GU base pairs are ubiquitous throughout RNA secondary structure. Within helical regions of RNA, GU base pairs tend to adhere to the canonical wobble structure. However, the structure of GU pairs adjacent to loop regions can differ from wobble structure. This ability to behave in different ways makes loops flanked by GU pairs difficult to predict and/or model. Here, GU pairs near 2 x 2 nucleotide internal loops were investigated both thermodynamically and structurally. A previous report of thermodynamic data showed that internal loops flanked by GU pairs displayed a large range of stabilities. NMR and melting studies showed that the large range was due to unexpected equilibria between hairpin and internal loop conformation within the pool of self-complementary RNA sequences. New non self complementary sequences were designed for proper measurement of GU flanked 2 x 2 internal loop thermodynamics. These new sequences demonstrated that internal loops flanked by GU pairs tend to be less favorable than expected. This result can lead to more accurate predictions of RNA secondary structure in the future. The new non self complementary sequences were examined structurally with NMR, in order to determine the reasons for their instability. NMR revealed a sequence dependent mix of 2 x 2 internal loops flanked by canonical wobble GU pairs and 2 x 2 internal loops with unexpected structures near the internal loop. For example, the 5'-GCUU/3'-UUCG internal loop has a GU conformation with a bifurcated hydrogen bond, in which U's O2 carbonyl inserts itself between G's amino and imino protons. The internal loop of 5'-GUCU/3'-UCUG displays a shifted configuration in which GC pairs flank a U-U pair and several U's are in fast exchange between positions inside and outside of the helix. Such unusual structures could serve as recognition elements for biological function and as benchmarks for structure prediction methods.

ISBN: 9781392007044Subjects--Topical Terms:

530508
Genetics.

Thermodynamic and Structural Studies of RNA Internal Loops Closed by GU Pairs.
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100 1 $a Berger, Kyle D. $3 3540416
245 1 0 $a Thermodynamic and Structural Studies of RNA Internal Loops Closed by GU Pairs.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 185 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-10, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Turner, Douglas H.
502 $a Thesis (Ph.D.)--University of Rochester, 2019.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be added to any third party search indexes.
506 $a This item must not be sold to any third party vendors.
520 $a The structure of RNA is largely dictated by its base to base interactions. GU base pairs are ubiquitous throughout RNA secondary structure. Within helical regions of RNA, GU base pairs tend to adhere to the canonical wobble structure. However, the structure of GU pairs adjacent to loop regions can differ from wobble structure. This ability to behave in different ways makes loops flanked by GU pairs difficult to predict and/or model. Here, GU pairs near 2 x 2 nucleotide internal loops were investigated both thermodynamically and structurally. A previous report of thermodynamic data showed that internal loops flanked by GU pairs displayed a large range of stabilities. NMR and melting studies showed that the large range was due to unexpected equilibria between hairpin and internal loop conformation within the pool of self-complementary RNA sequences. New non self complementary sequences were designed for proper measurement of GU flanked 2 x 2 internal loop thermodynamics. These new sequences demonstrated that internal loops flanked by GU pairs tend to be less favorable than expected. This result can lead to more accurate predictions of RNA secondary structure in the future. The new non self complementary sequences were examined structurally with NMR, in order to determine the reasons for their instability. NMR revealed a sequence dependent mix of 2 x 2 internal loops flanked by canonical wobble GU pairs and 2 x 2 internal loops with unexpected structures near the internal loop. For example, the 5'-GCUU/3'-UUCG internal loop has a GU conformation with a bifurcated hydrogen bond, in which U's O2 carbonyl inserts itself between G's amino and imino protons. The internal loop of 5'-GUCU/3'-UCUG displays a shifted configuration in which GC pairs flank a U-U pair and several U's are in fast exchange between positions inside and outside of the helix. Such unusual structures could serve as recognition elements for biological function and as benchmarks for structure prediction methods.
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