Title:
RNA and Metals as a Window onto Ancient Biochemistry

dc.contributor.advisor Williams, Loren D.
dc.contributor.advisor Glass, Jennifer B.
dc.contributor.author Guth-Metzler, Rebecca
dc.contributor.committeeMember Hud, Nicholas
dc.contributor.committeeMember Reddi, Amit
dc.contributor.committeeMember Wartell, Roger
dc.contributor.department Chemistry and Biochemistry
dc.date.accessioned 2023-05-18T17:58:25Z
dc.date.available 2023-05-18T17:58:25Z
dc.date.created 2023-05
dc.date.issued 2023-04-30
dc.date.submitted May 2023
dc.date.updated 2023-05-18T17:58:25Z
dc.description.abstract RNA is one of life’s three essential biopolymers. RNA is so entrenched in biology that it is thought to have arisen near the origin of life itself. Work herein uses RNA’s ancient relationship with divalent metals (M²⁺) as a detective’s lens to peer back into time. RNA uses Mg²⁺ as its primary M²⁺ partner in modern life. However, RNA evolved when Fe²⁺ was more available, in a time before rising atmospheric oxygen caused Fe²⁺ to “rust out”. Moreover, Fe²⁺ exposed to oxygen forms free radicals that break down biomolecules including RNA. Our research shows that Fe²⁺ kept in anoxic conditions mimicking early Earth does not cause oxidation reactions, instead having the same reaction with RNA as does Mg²⁺. Reaction similarity of Fe²⁺ and Mg²⁺ adds to growing evidence that Fe²⁺ may have been an early binding partner of RNA, and that RNA adaption through swapping out M²⁺ to support RNA survival over billions of years. Moreover, Fe²⁺ may have accelerated early RNA evolution, allowing RNA to diversify and multiply. Yet, to RNA, M²⁺ is a double-edged sword. While M²⁺ ions catalyze RNA cleavage, shortening its lifetime, they also promote RNA folding, which in turn protects RNA from cleavage. We further combine these concepts into the following scheme: too little M²⁺ shortens RNA lifetime because there is no folding and therefore no cleavage protection, too much M²⁺ shortens RNA lifetime because cleavage overwhelms folding protection, but the in-between “Goldilocks peak” of moderate [M²⁺] is “just right”. We find RNA Goldilocks peaks that take on a variety of appearances, revealing unexpected complexity from the innate RNA-Mg²⁺ relationship. The average Goldilocks peak of modern RNA may reflect the metal conditions of its origin, giving a clearer picture of the environment where life emerged. The Goldilocks peak boost to RNA lifetime perhaps caused RNA to win out over competing polymers on early Earth, a possible explanation for why RNA is one of life’s universal biopolymers.
dc.description.degree Ph.D.
dc.format.mimetype application/pdf
dc.identifier.uri https://hdl.handle.net/1853/72094
dc.language.iso en_US
dc.publisher Georgia Institute of Technology
dc.subject RNA biochemistry
dc.subject bioinorganic chemistry
dc.subject astrobiology
dc.subject origins of life
dc.title RNA and Metals as a Window onto Ancient Biochemistry
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Williams, Loren D.
local.contributor.advisor Glass, Jennifer B.
local.contributor.corporatename College of Sciences
local.contributor.corporatename School of Chemistry and Biochemistry
relation.isAdvisorOfPublication 2886d5c2-dc71-4ca2-a4bf-efd1856ef0aa
relation.isAdvisorOfPublication 46762027-c870-495e-a053-b7b8ffdc0730
relation.isOrgUnitOfPublication 85042be6-2d68-4e07-b384-e1f908fae48a
relation.isOrgUnitOfPublication f1725b93-3ab8-4c47-a4c3-3596c03d6f1e
thesis.degree.level Doctoral
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