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Published on: December 13, 2014
Nonsense-mediated mRNA decay in humans at a glance
Tatsuaki Kurosaki1, Lynne E Maquat2
1Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA Center for RNA Biology, University of Rochester, Rochester, NY 14642, USA.
Abstract:
Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that typifies all eukaryotes examined to date. NMD surveys newly synthesized mRNAs and degrades those that harbor a premature termination codon (PTC), thereby preventing the production of truncated proteins that could result in disease in humans. This is evident from dominantly inherited diseases that are due to PTC-containing mRNAs that escape NMD. Although many cellular NMD targets derive from mistakes made during, for example, pre-mRNA splicing and, possibly, transcription initiation, NMD also targets ∼10% of normal physiological mRNAs so as to promote an appropriate cellular response to changing environmental milieus, including those that induce apoptosis, maturation or differentiation. Over the past ∼35 years, a central goal in the NMD field has been to understand how cells discriminate mRNAs that are targeted by NMD from those that are not. In this Cell Science at a Glance and the accompanying poster, we review progress made towards this goal, focusing on human studies and the role of the key NMD factor up-frameshift protein 1 (UPF1).
Insights
Nonsense-mediated mRNA decay (NMD) removes faulty mRNAs with premature stop codons, preventing disease. This vital quality control also regulates healthy gene expression, with UPF1 being a key factor.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic process.
- NMD degrades mRNAs with premature termination codons (PTCs), preventing disease-causing truncated proteins.
- NMD also regulates ~10% of normal mRNAs for cellular responses.
Purpose of the Study:
- To review progress in understanding how cells discriminate NMD targets.
- Focus on human studies and the role of up-frameshift protein 1 (UPF1).
Main Methods:
- Review of existing literature and research on NMD pathways.
- Focus on human genetic studies and molecular mechanisms.
- Examination of the function of UPF1 in NMD.
Main Results:
- NMD is crucial for preventing genetic diseases caused by PTCs.
- NMD plays a significant role in regulating gene expression and cellular responses.
- UPF1 is identified as a central factor in the NMD pathway.
Conclusions:
- Understanding NMD is key to comprehending gene regulation and disease prevention.
- UPF1's role is critical in distinguishing target mRNAs for decay.
- Further research on NMD mechanisms can lead to therapeutic insights.
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