Differential regulation of the Saccharomyces cerevisiae iron regulon by the nonsense- mediated mRNA decay pathway under iron scarcity
Year: 2026
Type: preprint
Abstract: The nonsense-mediated mRNA decay (NMD) pathway is a conserved eukaryotic pathway that targets mRNAs prematurely terminating translation. Some endogenous, non-erroneous mature mRNAs are regulated by the NMD pathway, depending on the cellular context and extracellular stimuli. Prior studies have implicated NMD in maintaining cellular iron homeostasis, though to what extent is unknown. In this study, the effects of NMD on iron scarcity were examined in wild-type and NMD mutant (upf1Δ) strains by examining growth, iron content via inductively coupled plasma mass spectrometry (ICP-MS), transcriptome-wide analysis of potential NMD targets, and further validation of identified potential NMD targets. We found that cells with a nonfunctional NMD ( upf1∆ ) pathway have impaired growth in iron scarcity compared to wild-type cells. The NMD mutant strain accumulated higher levels of intracellular iron than the wild-type in both normal growth conditions and iron deplete conditions. Transcriptional activators of the iron regulon, AFT1 and AFT2 were observed to be NMD targets depending on growth condition and iron availability. Downstream targets of AFT1/2 include the ferric-cupric reductases FRE1, FRE2 , FRE3 , and FRE4 ; these were found to produce multiple mRNA isoforms that were also subject to NMD-mediated regulation under iron sufficiency and scarcity. Growth conditions of the cells impact NMD-mediated expression of FRE1-4 mRNAs and elucidates a temporal relationship of NMD-mediated regulation dependent on the duration of iron scarcity.
Source: Research Square
Institution: Baylor University
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7222566149