Eukaryotic release factor 1 from Euplotes promotes frameshifting at premature stop codons in human cells.

Stefanov, Bozhidar-Adrian; Ajuh, Elvis; Allen, Sarah; Nowacki, Mariusz (2024). Eukaryotic release factor 1 from Euplotes promotes frameshifting at premature stop codons in human cells. iScience, 27(4) Elsevier 10.1016/j.isci.2024.109413

Preview

Text 1-s2.0-S2589004224006345-main.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC). Download (4MB) | Preview

Human physiology is highly susceptible to frameshift mutations within coding regions, and many hereditary diseases and cancers are caused by such indels. Presently, therapeutic options to counteract them are limited and, in the case of direct genome editing, risky. Here, we show that release factor 1 (eRF1) from Euplotes, an aquatic protist known for frequent +1 frameshifts in its coding regions, can enhance +1 ribosomal frameshifting at slippery heptameric sequences in human cells without an apparent requirement for an mRNA secondary structure. We further show an increase in frameshifting rate at the premature termination sequence found in the HEXA gene of Tay-Sachs disease patients, or a breast cancer cell line that harbors a tumor-driving frameshift mutation in GATA3. Although the overall increase in frameshifting would need further improvement for clinical applications, our results underscore the potential of exogenous factors, such as Eu eRF1, to increase frameshifting in human cells.

Interest & Impact

Downloads

0 since deposited on 25 Mar 2024
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item