Time-Resolved, Single-Molecule, Correlated Chemical Probing of RNA.


Journal

Journal of the American Chemical Society
ISSN: 1520-5126
Titre abrégé: J Am Chem Soc
Pays: United States
ID NLM: 7503056

Informations de publication

Date de publication:
04 11 2020
Historique:
pubmed: 24 10 2020
medline: 15 4 2021
entrez: 23 10 2020
Statut: ppublish

Résumé

Capturing the folding dynamics of large, functionally important RNAs has relied primarily on global measurements of structure or on per-nucleotide chemical probing. These approaches infer, but do not directly measure, through-space structural interactions. Here we introduce trimethyloxonium (TMO) as a chemical probe for RNA. TMO alkylates RNA at high levels in seconds, and thereby enables time-resolved, single-molecule, through-space probing of RNA folding using the RING-MaP correlated chemical probing framework. Time-resolved correlations in the RNase P RNA-a functional RNA with a complex structure stabilized by multiple noncanonical interactions-revealed that a long-range tertiary interaction guides native RNA folding for both secondary and tertiary structure. This unanticipated nonhierarchical folding mechanism was directly validated by examining the consequences of concise disruption of the through-space interaction. Single-molecule, time-resolved RNA structure probing with TMO is poised to reveal a wide range of dynamic RNA folding processes and principles of RNA folding.

Identifiants

pubmed: 33095984
doi: 10.1021/jacs.0c06221
pmc: PMC7917579
mid: NIHMS1671766
doi:

Substances chimiques

Onium Compounds 0
Sulfuric Acid Esters 0
RNA 63231-63-0
Ribonuclease P EC 3.1.26.5
dimethyl sulfate JW5CW40Z50
trimethyloxonium RG47L030LR

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

18735-18740

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL111527
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122532
Pays : United States

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Auteurs

Jeffrey E Ehrhardt (JE)

Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, United States.

Kevin M Weeks (KM)

Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, United States.

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Classifications MeSH