Nonsense-mediated mRNA decay of metal-binding activator MAC1 is dependent on copper levels and 3′-UTR length in Saccharomyces cerevisiae.
Year: 2023
Type: preprint
Abstract: The nonsense-mediated mRNA decay (NMD) pathway was initially identified as a surveillance pathway that degrades mRNAs containing premature termination codons (PTCs). NMD is now also recognized as a post-transcriptional regulatory pathway that regulates the expression of natural mRNAs. Earlier studies demonstrated that regulation of functionally related natural mRNAs by NMD can be differential and condition-specific in Saccharomyces cerevisiae . Here, we investigated the regulation of MAC1 mRNAs by NMD in response to copper as well as the role which the MAC1 3′-UTR plays in this regulation. MAC1 is a copper-sensing transcription factor that regulates high-affinity copper transport and is activated under low copper conditions in S. cerevisiae . We discovered that MAC1 mRNAs are regulated by NMD under complete minimal (CM) but escaped NMD under low and high copper conditions. Mac1p-regulated genes escape NMD in conditions where MAC1 mRNAs are NMD sensitive. We also found that the MAC1 3′-UTR is the NMD targeting feature on the mRNAs, and that MAC1 mRNAs lacking 3′-UTRs were stabilized during copper deprivation. Our results demonstrate a mechanism of regulation for a metal-sensing transcription factor, at both the post-transcriptional and post-translational levels, where MAC1 mRNA levels are regulated by NMD and copper, while the activity of Mac1p is controlled by copper levels.
Authors: Bessie Kebaara, Xinyi Zhang
Institution: Baylor University
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4368365389