Real-time imaging of transcriptional feedback in nonsense-mediated mRNA decay

Abstract

Nonsense-mediated mRNA decay (NMD) is a translation-coupled mRNA decay pathway triggered by a premature termination codon (PTC). While in-frame stop codons are typically defined by cytoplasmic ribosomes, unexpected changes in transcription have been reported in genes containing PTCs. This observation suggests the possibility of PTC detection at the transcription site, which has not been thoroughly investigated with high temporal and spatial resolution. Here, we utilize a real-time imaging approach to simultaneously detect transcription sites expressing wild-type or NMD-targeted {beta}-globin reporter genes in the same cell. Our data indicates a dynamic change in the transcription of PTC-containing {beta}-globin mRNA that depends on translation, NMD, and nuclear protein import, supporting the existence of rapid transcriptional feedback following NMD in the cytoplasm. This study establishes a robust temporal link between cytoplasmic mRNA decay and nuclear transcription. One-Sentence SummaryLive-cell imaging shows that nonsense-mediated mRNA decay triggers a transcriptional feedback loop.