Cross-chiral exponential amplification of an RNA enzyme.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
29 Oct 2024
Historique:
medline: 22 10 2024
pubmed: 22 10 2024
entrez: 22 10 2024
Statut: ppublish

Résumé

An RNA ligase ribozyme that catalyzes the joining of RNA molecules of the opposite chiral handedness was optimized for the ability to synthesize its own enantiomer from two component fragments. The mirror-image D- and L-ligases operate in concert to provide a system for cross-chiral replication, whereby they catalyze each other's synthesis and undergo mutual amplification at constant temperature, with apparent exponential growth and a doubling time of about 1 h. Neither the D- nor the L-RNA components alone can achieve autocatalytic self-replication. Cross-chiral exponential amplification can be continued indefinitely through a serial-transfer process that provides an ongoing supply of the component D- and L-substrates. Unlike the familiar paradigm of semiconservative nucleic acid replication that relies on Watson-Crick pairing between complementary strands, cross-chiral replication relies on tertiary interactions between structured nucleic acids "across the mirror." There are few examples, outside of biology, of autocatalytic self-replication systems that undergo exponential amplification and there are no prior examples, in either biological or chemical systems, of cross-chiral replication enabling exponential amplification.

Identifiants

pubmed: 39436654
doi: 10.1073/pnas.2413668121
doi:

Substances chimiques

RNA, Catalytic 0
RNA Ligase (ATP) EC 6.5.1.3
RNA 63231-63-0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2413668121

Subventions

Organisme : NSF (NSF)
ID : MCB2114588
Organisme : HHS | NIH | National Institute of General Medical Sciences (NIGMS)
ID : F32GM146435

Déclaration de conflit d'intérêts

Competing interests statement:The authors declare no competing interest.

Auteurs

Wesley G Cochrane (WG)

The Salk Institute, La Jolla, CA 92037.

Grant A L Bare (GAL)

The Salk Institute, La Jolla, CA 92037.

Gerald F Joyce (GF)

The Salk Institute, La Jolla, CA 92037.

David P Horning (DP)

The Salk Institute, La Jolla, CA 92037.

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Classifications MeSH