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Lookup NU author(s): Dr Soren NielsenORCiD, Professor Nikolay ZenkinORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2025 The Authors, some rights reserved. RNA polymerase I (Pol I) synthesizes ribosomal RNA precursor (pre-rRNA), which comprises most of RNA in eukaryotic cells. Despite decades of investigation, there is still no consensus on what causes Pol I transcription termination. Here, we show that efficient termination by Pol I, paused by termination roadblock protein, is caused by RNA hairpin of the nascent pre-rRNA. Hairpin-dependent termination takes place at a physiological rate and does not require trans-acting factors. The function of the roadblock protein and the T-rich sequence is to synergistically cause deep backtracking of Pol I toward the termination RNA hairpin. Simultaneously, Pol I is catalytically inactivated, preventing rescue from backtracking through RNA cleavage and thus committing Pol I to termination. Termination RNA hairpins are present in most of Pol I terminators of eukaryotes, suggesting conservation of the RNA hairpin–dependent mechanism of Pol I transcription termination. We propose a simple model that unifies previous findings.
Author(s): Nielsen S, Zenkin N
Publication type: Article
Publication status: Published
Journal: Science Advances
Year: 2025
Volume: 11
Issue: 34
Print publication date: 22/08/2025
Online publication date: 20/08/2025
Acceptance date: 18/07/2025
Date deposited: 01/09/2025
ISSN (electronic): 2375-2548
Publisher: American Association for the Advancement of Science
URL: https://doi.org/10.1126/sciadv.adw2470
DOI: 10.1126/sciadv.adw2470
Data Access Statement: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. All data presented are included in the paper, and no other dataset, code, or method is used.
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