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.
Bibliographical noteFunding Information:
Funding: This work was supported by an NRF (National Research Foundation) of Korea grant funded by the Korean government (Ministry of Science, ICT, and Future Planning; NRF-2015R1A3A2033665 and 2018R1A5A1024261) and by a Korea University grant.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- MRNA surveillance
- Nonsense-mediated mRNA decay
- Protein quality control
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)