RNA modifications stabilize the tertiary structure of tRNAfMet by locally increasing conformational dynamics

  • A plethora of modified nucleotides extends the chemical and conformational space for natural occurring RNAs. tRNAs constitute the class of RNAs with the highest modification rate. The extensive modification modulates their overall stability, the fidelity and efficiency of translation. However, the impact of nucleotide modifications on the local structural dynamics is not well characterized. Here we show that the incorporation of the modified nucleotides in tRNAfMet from Escherichia coli leads to an increase in the local conformational dynamics, ultimately resulting in the stabilization of the overall tertiary structure. Through analysis of the local dynamics by NMR spectroscopic methods we find that, although the overall thermal stability of the tRNA is higher for the modified molecule, the conformational fluctuations on the local level are increased in comparison to an unmodified tRNA. In consequence, the melting of individual base pairs in the unmodified tRNA is determined by high entropic penalties compared to the modified. Further, we find that the modifications lead to a stabilization of long-range interactions harmonizing the stability of the tRNA’s secondary and tertiary structure. Our results demonstrate that the increase in chemical space through introduction of modifications enables the population of otherwise inaccessible conformational substates.

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Author:Thomas BiedenbänderORCiD, Vanessa de JesusORCiDGND, Martina Schmidt-DenglerORCiD, Mark HelmORCiDGND, Björn CorziliusORCiDGND, Boris FürtigORCiDGND
URN:urn:nbn:de:hebis:30:3-751323
DOI:https://doi.org/10.1093/nar/gkac040
ISSN:1362-4962
Parent Title (English):Nucleic acids research
Publisher:Oxford Univ. Press
Place of publication:Oxford
Document Type:Article
Language:English
Date of Publication (online):2022/02/07
Date of first Publication:2022/02/07
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/07/15
Volume:50
Issue:4
Page Number:16
First Page:2334
Last Page:2349
Note:
Chemical shifts and relaxation data are deposited at BMRB under accession code 51144.
Note:
Funding for open access charge: University Frankfurt.
Note:
Funding: HMWK
HeBIS-PPN:521813255
Institutes:Biochemie, Chemie und Pharmazie
Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International