UPF1: From mRNA Surveillance to Protein Quality Control
Hyun Jung Hwang, Yeonkyoung Park, Yoon Ki Kim
Abstract
Selective recognition and removal of faulty transcripts and misfolded polypeptides are crucial for cell viability. In eukaryotic cells, nonsense-mediated mRNA decay (NMD) constitutes an mRNA surveillance pathway for sensing and degrading aberrant transcripts harboring premature termination codons (PTCs). NMD functions also as a post-transcriptional gene regulatory mechanism by downregulating naturally occurring mRNAs. As NMD is activated only after a ribosome reaches a PTC, PTC-containing mRNAs inevitably produce truncated and potentially misfolded polypeptides as byproducts. To cope with the emergence of misfolded polypeptides, eukaryotic cells have evolved sophisticated mechanisms such as chaperone-mediated protein refolding, rapid degradation of misfolded polypeptides through the ubiquitin-proteasome system, and sequestration of misfolded polypeptides to the aggresome for autophagy-mediated degradation. In this review, we discuss how UPF1, a key NMD factor, contributes to the selective removal of faulty transcripts via NMD at the molecular level. We then highlight recent advances on UPF1-mediated communication between mRNA surveillance and protein quality control.