Determining the effects of pseudouridine incorporation on human tRNAs

Title (eng)
Determining the effects of pseudouridine incorporation on human tRNAs
Author
Anna Biela
Author
Jakub Nowak
Author
Artur Biela
Author
Sunandan Mukherjee
Author
Seyed Naeim Moafinejad
Author
Satyabrata Maiti
Author
Andrzej Chramiec-Glabik
Author
Rahul Mehta
Author
Jakub Jezowski
Author
Dominika Dobosz
Author
Priyanka Dahate
Author
Veronique Arluison
Author
Frank Wien
Author
Paulina Indyka
Author
Michal Rawski
Author
Janusz M. Bujnicki
Author
Ting-Yu Lin
Abstract (eng)
Transfer RNAs (tRNAs) are ubiquitous non-coding RNA molecules required to translate mRNA-encoded sequence information into nascent polypeptide chains. Their relatively small size and heterogenous patterns of their RNA modifications have impeded the systematic structural characterization of individual tRNAs. Here, we use single-particle cryo-EM to determine the structures of four human tRNAs before and after incorporation of pseudouridines (Ψ). Following post-transcriptional modifications by distinct combinations of human pseudouridine synthases, we find that tRNAs become stabilized and undergo specific local structural changes. We establish interactions between the D- and T-arms as the key linchpin in the tertiary structure of tRNAs. Our structures of human tRNAs highlight the vast potential of cryo-EM combined with biophysical measurements and computational simulations for structure-function analyses of tRNAs and other small, folded RNA domains.
Keywords (eng)
tRNACryo-EMRNA ModificationsRNA FoldingMolecular Dynamics Simulation
Type (eng)
Language
[eng]
Is in series
Title (eng)
EMBO Journal
Volume
44
Issue
13
ISSN
1460-2075
Issued
2025
Number of pages
33
Publication
Wiley
Date issued
2025
Access rights (eng)
Rights statement (eng)
© 2025 The Author(s)