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X Marks the Spot: The Biophysical Ch...

Sperstad, Parker D.,

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X Marks the Spot: The Biophysical Characterization of an Untranslated Riboregulatory Element From the Hepatitis C Virus Genome /

Record Type:	Electronic resources : Monograph/item
Title/Author:	X Marks the Spot: The Biophysical Characterization of an Untranslated Riboregulatory Element From the Hepatitis C Virus Genome // Parker D Sperstad.
Author:	Sperstad, Parker D.,
Description:	1 electronic resource (159 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-07, Section: B.
Contained By:	Dissertations Abstracts International86-07B.
Subject:	Biochemistry. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31764801
ISBN:	9798302830890

X Marks the Spot: The Biophysical Characterization of an Untranslated Riboregulatory Element From the Hepatitis C Virus Genome /
Sperstad, Parker D.,

X Marks the Spot: The Biophysical Characterization of an Untranslated Riboregulatory Element From the Hepatitis C Virus Genome /Parker D Sperstad. - 1 electronic resource (159 pages)

Source: Dissertations Abstracts International, Volume: 86-07, Section: B.

The central dogma of molecular biology states that DNA is transcribed into RNA that is then translated into protein. Most molecular biology research focuses on the two end points of this central dogma, with RNA being the middleman that carries genetic information from long term storage - DNA - to active workers of the cells - protein. Commonly portrayed as a simple messenger, the discovery of enzymatic RNA molecules (ribozymes) by Cech and Altman in the early 1980s was the first characterization of the many alternative functions that RNA can perform. Much like functional proteins of the cell, these RNA molecules are only active when they adopt a specific three-dimensional structure. This dissertation focuses on a category of non-protein coding RNA molecules that regulate various aspects of viral infections.In 2020 the Nobel Prize in Physiology or Medicine was awarded to Harvey J. Alter, Michael Houghton, and Charles M. Rice for their work studying the hepatitis C virus (HCV). Alter originally reported on a hepatitis viral infection that was not caused by hepatitis A or hepatitis B viruses in the early 1970s, which was later identified by Houghton in 1989. For the next several years, labs struggled to study HCV as there was no established cell culture system that could reliably replicate the virus. This was all believed to be due to a missing sequence at the very 3' end of the RNA genome. This region of the genome was called 3'X as it was the only unknown variable left unsequenced. In the mid 1990s, two groups published sequencing results for this RNA within a year of one another: the Shimotohno Lab from Japan in 1995 and the Rice Lab from the United States in 1996. The next year, the Rice lab was able to infect chimpanzees with viral transcripts that included this otherwise missing sequence. This paved the way to effective cell culture systems and, eventually, the development of anti-viral therapeutics.Even though there are now several reliable cell systems to study HCV infection, it remains unclear as to how this relatively short, untranslated RNA is required for viral replication. Specifically, the exact structure of 3'X and the mechanisms of its various binding interactions have yet to be resolved. This dissertation describes our efforts to address these gaps in knowledge. Chapter one provides an introduction to HCV biochemistry and the critically important 3'X RNA, setting the stage for my contributions to the relevant fields. Chapter two provides an overview of the experimental methods employed during this work. Chapter three highlights our findings regarding the structural heterogeneity and conformational dynamics of monomeric 3'X RNA. Chapter four details the mechanism governing the spontaneous dimerization 3'X RNA. Lastly, chapter five is an appendix that documents some of our early unpublished experimental results and newly developing projects. The latter provide excellent starting points for future research efforts involving this fascinating RNA.

English

ISBN: 9798302830890Subjects--Topical Terms:

518028
Biochemistry.
Subjects--Index Terms:

Dynamics

X Marks the Spot: The Biophysical Characterization of an Untranslated Riboregulatory Element From the Hepatitis C Virus Genome /
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500 $a Source: Dissertations Abstracts International, Volume: 86-07, Section: B.
500 $a Advisors: Holmstrom, Erik D. Committee members: Berrie, Cindy L.; De Guzman, Roberto N.; Fehr, Anthony R.; Kuczera, Krzysztof.
502 $b Ph.D. $c University of Kansas $d 2024.
520 $a The central dogma of molecular biology states that DNA is transcribed into RNA that is then translated into protein. Most molecular biology research focuses on the two end points of this central dogma, with RNA being the middleman that carries genetic information from long term storage - DNA - to active workers of the cells - protein. Commonly portrayed as a simple messenger, the discovery of enzymatic RNA molecules (ribozymes) by Cech and Altman in the early 1980s was the first characterization of the many alternative functions that RNA can perform. Much like functional proteins of the cell, these RNA molecules are only active when they adopt a specific three-dimensional structure. This dissertation focuses on a category of non-protein coding RNA molecules that regulate various aspects of viral infections.In 2020 the Nobel Prize in Physiology or Medicine was awarded to Harvey J. Alter, Michael Houghton, and Charles M. Rice for their work studying the hepatitis C virus (HCV). Alter originally reported on a hepatitis viral infection that was not caused by hepatitis A or hepatitis B viruses in the early 1970s, which was later identified by Houghton in 1989. For the next several years, labs struggled to study HCV as there was no established cell culture system that could reliably replicate the virus. This was all believed to be due to a missing sequence at the very 3' end of the RNA genome. This region of the genome was called 3'X as it was the only unknown variable left unsequenced. In the mid 1990s, two groups published sequencing results for this RNA within a year of one another: the Shimotohno Lab from Japan in 1995 and the Rice Lab from the United States in 1996. The next year, the Rice lab was able to infect chimpanzees with viral transcripts that included this otherwise missing sequence. This paved the way to effective cell culture systems and, eventually, the development of anti-viral therapeutics.Even though there are now several reliable cell systems to study HCV infection, it remains unclear as to how this relatively short, untranslated RNA is required for viral replication. Specifically, the exact structure of 3'X and the mechanisms of its various binding interactions have yet to be resolved. This dissertation describes our efforts to address these gaps in knowledge. Chapter one provides an introduction to HCV biochemistry and the critically important 3'X RNA, setting the stage for my contributions to the relevant fields. Chapter two provides an overview of the experimental methods employed during this work. Chapter three highlights our findings regarding the structural heterogeneity and conformational dynamics of monomeric 3'X RNA. Chapter four details the mechanism governing the spontaneous dimerization 3'X RNA. Lastly, chapter five is an appendix that documents some of our early unpublished experimental results and newly developing projects. The latter provide excellent starting points for future research efforts involving this fascinating RNA.
546 $a English
590 $a School code: 0099
650 4 $a Biochemistry. $3 518028
650 4 $a Biophysics. $3 518360
653 $a Dynamics
653 $a Hepatitis C virus
653 $a Structures
690 $a 0487
690 $a 0786
710 2 $a University of Kansas. $b Molecular Biosciences. $e degree granting institution. $3 3828569
720 1 $a Holmstrom, Erik D. $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 86-07B.
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791 $a Ph.D.
792 $a 2024
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31764801