# Nonsense-Mediated mRNA Decay: Mechanism and Function ## Introduction to Nonsense-Mediated mRNA Decay Nonsense-mediated mRNA decay (NMD) is a highly conserved RNA surveillance pathway that selectively degrades messenger RNAs (mRNAs) harboring premature termination codons (PTCs). A PTC is an in-frame stop codon that appears upstream of the normal [termination codon](/knowledge/molecular-biology/termination-codon), and its presence almost always results from a nonsense mutation, a [frameshift mutation](/knowledge/molecular-biology/frameshift-mutation), or errors in [mRNA splicing](/knowledge/molecular-biology/mrna-splicing). If translated, such transcripts would produce truncated proteins with potentially dominant-negative or gain-of-function activities—outcomes that are generally deleterious to cellular homeostasis. The fundamental purpose of NMD is therefore twofold: it prevents the synthesis of C-terminally truncated polypeptides, and it eliminates aberrant transcripts from the cellular pool. Beyond this quality-control role, NMD also regulates the expression of a substantial fraction of the transcriptome. It is estimated that 5–10% of all human mRNAs are natural NMD substrates, including transcripts with upstream open reading frames (uORFs), selenoprotein mRNAs, and alternatively spliced isoforms containing PTCs. This places NMD at the center of post-transcriptional gene regulation, with significant consequences for development, stress responses, and disease pathogenesis. NMD is mechanistically coupled to translation. The pathway is triggered when the ribosome encounters a stop codon that is recognized as premature, a distinction that depends on the spatial relationship between the terminating ribosome and downstream mRNA features. In mammals, the most well-characterized marker of a "normal" termination context is the exon junction complex (EJC), a multi-protein assembly deposited on mRNA during splicing. The presence of an EJC downstream of a stop codon marks that stop as premature, whereas a stop codon in the terminal exon—with no downstream EJC—is recognized as normal. This simple geometric rule, refined by additional layers of regulation, forms the basis of PTC recognition in higher eukaryotes. The clinical importance of NMD cannot be overstated. Approximately one-third of all inherited human genetic disorders are caused by nonsense or frameshift mutations that generate PTCs. The severity of these diseases is often modulated by the efficiency of NMD: transcripts that escape NMD produce truncated proteins that may retain partial function (resulting in milder phenotypes) or exert dominant-negative effects (resulting in more severe phenotypes). Understanding NMD is therefore not only a matter of fundamental molecular biology but also a prerequisite for developing therapeutic strategies, including readthrough drugs and NMD inhibitors, for a wide range of genetic diseases. ## The NMD Pathway: Key Players and Steps The core NMD machinery comprises three conserved UPF (up-frameshift) proteins—UPF1, UPF2, and UPF3—along with the SMG (suppressor with morphogenetic effect on genitalia) family of proteins that regulate UPF1 phosphorylation and dephosphorylation. These factors assemble on the mRNA in a coordinated sequence of events that ultimately commits the transcript to degradation. ### Exon Junction Complex (EJC) The EJC is a multi-subunit protein complex deposited ~20–24 nucleotides upstream of exon–exon junctions during [mRNA splicing](/knowledge/molecular-biology/mrna-splicing). Its core components are eIF4AIII (a DEAD-box RNA helicase), Y14 (RBM8A), and MAGOH. eIF4AIII binds the RNA backbone in an ATP-dependent manner, while Y14 and MAGOH lock the complex in place by preventing ATP hydrolysis. The peripheral factors UPF3B and RNPS1 are recruited to the core EJC during splicing, and UPF2 associates with the complex in the cytoplasm. The EJC serves as the primary molecular landmark for PTC recognition in mammals. During the pioneer round of translation—the first translation event on a newly exported mRNA—the ribosome traverses the transcript and displaces EJCs as it moves. If the ribosome encounters a stop codon before all EJCs have been removed, the remaining downstream EJCs recruit the NMD machinery. In contrast, a normal stop codon is typically located in the last exon, and by the time the ribosome reaches it, all EJCs have been displaced. This "EJC rule" explains why PTCs located more than 50–55 nucleotides upstream of the last exon–exon junction efficiently trigger NMD, while PTCs in the terminal exon do not. ### Recognition of Premature Termination Codons The recognition of a PTC begins when the ribosome stalls at a stop codon with a downstream EJC. The translation termination factors eRF1 (eukaryotic release factor 1) and eRF3 (eukaryotic release factor 3) normally bind the stop codon and promote peptide release. However, in the presence of a downstream EJC, this termination event is aberrant. The key event is the recruitment of UPF1, an ATP-dependent RNA helicase and the central regulator of NMD. UPF1 is a phosphoprotein that cycles between phosphorylated and dephosphorylated states. In its unphosphorylated form, UPF1 associates with the translating ribosome via its interaction with eRF3. When the ribosome terminates at a PTC, UPF1 remains associated with the release factors and is positioned to interact with the EJC-bound UPF2–UPF3 complex. This interaction triggers the phosphorylation of UPF1 by SMG1, a phosphatidylinositol 3-kinase-related kinase (PIKK) family member. SMG1 is part of a larger complex called the SURF complex (SMG1–UPF1–eRF1–eRF3), which forms at the stalled ribosome. The phosphorylation of UPF1 at multiple serine/threonine residues (notably Ser1078, Ser1096, and Thr1123 in human UPF1) is the committed step in NMD activation. Phosphorylated UPF1 undergoes a conformational change that activates its [helicase activity](/knowledge/molecular-biology/helicase-activity), allowing it to remodel the mRNA–protein complex and recruit downstream decay factors. The phosphorylation also stabilizes the interaction between UPF1 and the EJC, ensuring that the NMD response is robust and processive. ## Mechanisms of PTC Recognition While the EJC-dependent model is the best-characterized mechanism of PTC recognition in mammals, it is not the only one. NMD can also occur in the absence of EJCs, particularly in organisms like yeast that lack the EJC entirely, and in mammalian cells for certain transcripts. Understanding both mechanisms is essential for a complete picture of NMD. ### EJC-Dependent Recognition In the EJC-dependent pathway, the critical determinant is the presence of at least one EJC downstream of the terminating ribosome. The molecular events proceed as follows: 1. The ribosome terminates at a PTC located ≥50–55 nucleotides upstream of an exon–exon junction. 2. eRF1 and eRF3 bind the stop codon, and UPF1 is recruited via its interaction with eRF3. 3. The SURF complex (SMG1–UPF1–eRF1–eRF3) forms at the stalled ribosome. 4. The EJC-bound UPF2–UPF3 complex interacts with UPF1, bridging the gap between the terminating ribosome and the downstream EJC. 5. SMG1 phosphorylates UPF1, activating the NMD response. 6. Phosphorylated UPF1 recruits SMG5, SMG6, and SMG7, which promote mRNA degradation. The distance requirement of ~50–55 nucleotides is thought to reflect the physical space needed for the ribosome to clear the exon–exon junction and for the EJC to remain accessible. If the PTC is too close to the junction, the ribosome may displace the EJC during translation, and NMD is not triggered. ### EJC-Independent Recognition EJC-independent NMD operates through alternative mechanisms that do not rely on exon–exon junctions. These pathways are particularly important in organisms like *Saccharomyces cerevisiae*, which lack the EJC, and in mammalian cells for transcripts that are not spliced or that have PTCs in the last exon. Several features can mark a stop codon as premature in the absence of an EJC: - **Long 3' untranslated regions (3' UTRs):** A stop codon followed by an abnormally long 3' UTR (>300 nucleotides in yeast, >1000 nucleotides in mammals) can trigger NMD. This is thought to occur because the normal interaction between the terminating ribosome and the poly(A)-binding protein (PABPC1) is disrupted when the 3' UTR is too long. In normal termination, PABPC1 bound to the poly(A) tail interacts with eRF3 to promote efficient termination and protect the mRNA from NMD. When the 3' UTR is excessively long, this interaction is lost, and the termination event is recognized as aberrant. - **UPF1 binding to the 3' UTR:** In some cases, UPF1 can bind directly to the 3' UTR of mRNAs, particularly those with complex or structured 3' UTRs. This binding can recruit the NMD machinery even in the absence of an EJC. - **uORFs and selenoprotein mRNAs:** Transcripts with upstream open reading frames (uORFs) are natural NMD substrates. When the ribosome translates a uORF and terminates at its stop codon, the downstream main ORF is not yet translated, and the termination event is recognized as premature. Similarly, selenoprotein mRNAs contain a selenocysteine insertion sequence (SECIS) element in their 3' UTR that is required for the recoding of UGA as selenocysteine. When selenium is limiting, the ribosome stalls at UGA, and the transcript is targeted for NMD. The EJC-independent pathway is less well understood mechanistically, but it is clear that the common theme is the disruption of normal termination fidelity. Any condition that prevents the proper interaction between the terminating ribosome, release factors, and PABPC1 can mark a stop codon as premature. ## Downstream Events: mRNA Degradation Once UPF1 is phosphorylated, the mRNA is committed to degradation. The decay phase of NMD is mediated by several downstream effectors that are recruited by phosphorylated UPF1. These effectors can be divided into two broad categories: those that promote endonucleolytic cleavage and those that promote exonucleolytic decay. ### Endonucleolytic Cleavage SMG6 is an endonuclease that cleaves the mRNA in the vicinity of the PTC. SMG6 contains a PIN (PilT N-terminus) domain with endonucleolytic activity, and it is recruited to the NMD complex through its interaction with phosphorylated UPF1. The cleavage site is typically located 5–50 nucleotides downstream of the PTC, and the resulting cleavage products are rapidly degraded by exonucleases. The endonucleolytic cleavage by SMG6 is a rapid and efficient mechanism of mRNA destruction. It does not require prior deadenylation or decapping, making it distinct from the general mRNA decay pathways. The 5' cleavage product, which retains the 5' cap but lacks a poly(A) tail, is degraded by the exosome (3'→5' exonuclease complex), while the 3' cleavage product, which retains the poly(A) tail but lacks the cap, is degraded by XRN1 (5'→3' exonuclease). ### Exonucleolytic Decay In addition to SMG6-mediated cleavage, NMD can also promote mRNA degradation through the general mRNA decay machinery. Phosphorylated UPF1 recruits the SMG5–SMG7 heterodimer, which in turn recruits the CCR4–NOT deadenylase complex and the DCP1–DCP2 decapping complex. These complexes promote: 1. **Deadenylation:** The poly(A) tail is shortened by the CCR4–NOT complex, which contains the deadenylases CCR4 (CNOT6) and CAF1 (CNOT7/8). Deadenylation is often the rate-limiting step in mRNA decay. 2. **Decapping:** Once the poly(A) tail is sufficiently shortened, the 5' cap is removed by the DCP2 decapping enzyme, assisted by its cofactor DCP1 and the LSM1–7 complex. 3. **5'→3' exonucleolytic degradation:** The decapped mRNA is degraded by XRN1, a processive 5'→3' exonuclease that rapidly destroys the transcript. Alternatively, the deadenylated mRNA can be degraded in the 3'→5' direction by the exosome complex, with the 5' cap being removed by the scavenger decapping enzyme DCP-S (DCPS). The choice between SMG6-mediated endonucleolytic cleavage and SMG5/7-mediated exonucleolytic decay is not mutually exclusive, and both pathways can contribute to the degradation of a single transcript. The relative contribution of each pathway may vary depending on the transcript, the cell type, and the specific NMD trigger. ## Regulation of NMD NMD is not a constitutive, unregulated pathway. Its activity is modulated in response to developmental cues, cellular stress, and the expression of specific regulatory factors. This regulation is essential for the proper function of NMD in both quality control and gene expression control. ### Autoregulation of NMD Factors Several NMD factors are themselves subject to NMD regulation, creating negative feedback loops that maintain homeostasis. For example: - **UPF3B:** The UPF3B gene produces multiple alternatively spliced isoforms, some of which contain PTCs and are targeted by NMD. This creates an autoregulatory loop in which UPF3B protein levels control the abundance of its own mRNA. - **SMG5, SMG6, and SMG7:** The mRNAs encoding these proteins contain uORFs or other NMD-inducing features, making them natural NMD substrates. When NMD is active, these transcripts are degraded; when NMD is inhibited, their expression increases. - **PABPC1:** The poly(A)-binding protein mRNA contains a long 3' UTR that can trigger NMD under certain conditions, providing a link between translation status and NMD activity. This autoregulation ensures that NMD activity is tightly controlled and can be rapidly adjusted in response to changing cellular conditions. ### NMD and Disease NMD plays a dual role in genetic disease. On one hand, NMD protects cells from the deleterious effects of truncated proteins by degrading PTC-containing mRNAs. On the other hand, NMD can exacerbate disease by eliminating mRNAs that would otherwise produce partially functional proteins. The clinical outcome of a nonsense mutation often depends on whether the mutant transcript is degraded by NMD or escapes it: - **NMD-sensitive mutations:** If the PTC is located more than 50–55 nucleotides upstream of the last exon–exon junction, the transcript is efficiently degraded, and the result is a loss-of-function phenotype (haploinsufficiency). This is the case for many mutations in [tumor suppressor genes](/knowledge/molecular-biology/tumor-suppressor-gene) like *TP53* and *BRCA1*. - **NMD-escape mutations:** If the PTC is located in the last exon or within 50 nucleotides of the last exon–exon junction, the transcript escapes NMD and produces a truncated protein. These truncated proteins may retain partial function (resulting in milder phenotypes) or exert dominant-negative effects (resulting in more severe phenotypes). For example, certain *COL2A1* mutations that escape NMD cause more severe forms of achondrogenesis than those that are degraded. The modulation of NMD activity is therefore a potential therapeutic strategy. NMD inhibitors, such as the small molecule NMDI-14, have been shown to restore the expression of PTC-containing mRNAs in cellular models of cystic fibrosis and Duchenne muscular dystrophy. Conversely, enhancing NMD activity could be beneficial in diseases where truncated proteins are toxic, such as some forms of dominant-negative inherited disorders. ## Methods to Study NMD Studying NMD requires experimental approaches that can detect and quantify PTC-containing mRNAs and their decay rates. Several methods are commonly used, each with its own strengths and limitations. ### Reporter Constructs The classical approach to studying NMD involves the use of reporter constructs that contain a PTC in a well-defined context. A typical reporter consists of a constitutively active promoter (e.g., CMV or β-globin promoter) driving the expression of a reporter gene (e.g., firefly luciferase, GFP, or β-globin) with a PTC inserted at a specific position. The reporter is transfected into cells, and the steady-state mRNA level is measured by quantitative RT-PCR or Northern blotting. Key design considerations include: - **PTC position:** The PTC should be placed at least 50 nucleotides upstream of the last exon–exon junction to ensure efficient NMD. - **Control constructs:** A wild-type reporter (no PTC) and a PTC-containing reporter with the PTC in the last exon (NMD-insensitive) should be included as controls. - **Normalization:** The reporter mRNA levels should be normalized to a co-transfected control plasmid (e.g., Renilla luciferase) to account for transfection efficiency. For measuring decay rates, transcription can be shut off using actinomycin D (5 µg/mL) or by using a tetracycline-regulated promoter, and mRNA levels are measured at multiple time points (e.g., 0, 2, 4, 6, and 8 hours) to calculate the half-life. ### High-Throughput Techniques Recent advances in sequencing and [computational biology](/knowledge/bioinformatics/computational-approaches-to-understanding-antimicrobial-resistance-amr) have enabled genome-wide studies of NMD: - **RNA-seq:** Comparing the transcriptomes of control cells and cells with NMD factors knocked down (e.g., UPF1 siRNA) can identify endogenous NMD substrates. Transcripts that are upregulated upon UPF1 depletion are candidate NMD targets. This approach has identified hundreds of natural NMD substrates in human cells. - **[Ribosome profiling](/knowledge/molecular-biology/ribosome-profiling):** This technique involves deep sequencing of ribosome-protected mRNA fragments to map ribosome positions at single-nucleotide resolution. [Ribosome profiling](/knowledge/molecular-biology/ribosome-profiling) can identify PTCs by detecting ribosome stalling at premature stop codons and can distinguish NMD substrates from other transcripts. - **Crosslinking and immunoprecipitation (CLIP):** CLIP-seq with antibodies against UPF1 or other NMD factors can identify the direct binding sites of NMD proteins on mRNAs, providing mechanistic insights into PTC recognition. - **Inhibitor treatments:** Small molecule inhibitors of NMD, such as cycloheximide (which inhibits translation elongation) or emetine (which inhibits translation initiation), can be used to block NMD and stabilize PTC-containing mRNAs. These inhibitors are useful for validating NMD substrates but must be used with caution due to their broad effects on translation. ## Common Pitfalls and Misconceptions Students frequently encounter several conceptual difficulties when learning about NMD. Being aware of these pitfalls can prevent confusion and deepen understanding. **1. Confusing NMD with other RNA decay pathways.** NMD is specific for PTC-containing mRNAs and requires translation. It is distinct from general mRNA decay (which degrades all mRNAs), microRNA-mediated silencing (which inhibits translation and promotes deadenylation), and other quality-control pathways like no-go decay (which targets stalled ribosomes) and nonstop decay (which targets mRNAs lacking a stop codon). The key distinguishing feature of NMD is its dependence on UPF1 and the recognition of premature termination. **2. Assuming the EJC is required for all NMD.** While the EJC is the primary determinant of PTC recognition in mammals, NMD can occur without EJCs. Yeast lack the EJC entirely, and mammalian cells can trigger NMD through EJC-independent mechanisms such as long 3' UTRs. The EJC rule is a useful heuristic, but it is not absolute. **3. Thinking that NMD only degrades mutant mRNAs.** NMD also regulates the expression of many normal transcripts, including those with uORFs, alternatively spliced isoforms, and selenoprotein mRNAs. This regulatory function is essential for proper gene expression and is disrupted in various diseases. **4. Believing that all PTCs trigger NMD equally.** The efficiency of NMD depends on the position of the PTC relative to exon–exon junctions, the length of the 3' UTR, and the presence of NMD-enhancing or NMD-suppressing elements. Some PTCs are "NMD-escape" mutations that produce truncated proteins, and these can have different clinical consequences than NMD-sensitive mutations. **5. Misunderstanding the role of UPF1 phosphorylation.** UPF1 phosphorylation by SMG1 is a critical step in NMD activation, but it is not the only regulatory event. UPF1 must also be dephosphorylated by the PP2A complex (comprising SMG5, SMG6, and SMG7) for the pathway to recycle and for the cell to maintain NMD competence. The phosphorylation–dephosphorylation cycle is essential for NMD function. **6. Confusing the pioneer round of translation with steady-state translation.** NMD is coupled to the first (pioneer) round of translation, during which EJCs are still associated with the mRNA. Once the mRNA has undergone multiple rounds of translation, the EJCs are displaced, and the transcript is no longer a substrate for EJC-dependent NMD. This explains why NMD efficiency is influenced by translation initiation rates and why inhibitors of translation can block NMD. ## Summary and Clinical Relevance Nonsense-mediated mRNA decay is a translation-dependent surveillance pathway that degrades mRNAs containing premature termination codons. The pathway is initiated when the ribosome terminates at a stop codon that is recognized as premature, either because of a downstream EJC or because of other features such as a long 3' UTR. The central regulator of NMD is UPF1, whose phosphorylation by SMG1 commits the mRNA to degradation. Downstream decay is mediated by SMG6 (endonucleolytic cleavage) and SMG5/7 (exonucleolytic decay via deadenylation and decapping). NMD is not merely a quality-control mechanism; it is a critical regulator of gene expression that affects 5–10% of the transcriptome. Its activity is regulated in response to developmental cues, stress, and the expression of NMD factors themselves. In human disease, NMD plays a dual role: it protects cells from truncated proteins but can also exacerbate disease by eliminating partially functional mRNAs. Understanding NMD is therefore essential for both basic biology and clinical medicine. Therapeutic strategies targeting NMD are actively being developed. NMD inhibitors could restore the expression of PTC-containing mRNAs in diseases like cystic fibrosis and Duchenne muscular dystrophy, while NMD enhancers could be beneficial in diseases where truncated proteins are toxic. The success of these approaches will depend on a detailed understanding of NMD mechanisms and their regulation in different cellular contexts. ## Frequently Asked Questions ### What is nonsense-mediated mRNA decay? Nonsense-mediated mRNA decay (NMD) is a cellular surveillance pathway that recognizes and degrades messenger RNAs containing premature termination codons (PTCs). A PTC is a stop codon that appears before the normal termination codon, typically due to a nonsense or [frameshift mutation](/knowledge/molecular-biology/frameshift-mutation). NMD prevents the translation of these aberrant mRNAs into truncated proteins. ### What is the function of the nonsense-mediated mRNA decay process? NMD serves two primary functions. First, it acts as a quality-control mechanism that eliminates PTC-containing mRNAs, preventing the synthesis of truncated proteins that could be toxic or dominant-negative. Second, it regulates the expression of a substantial fraction of the transcriptome, including mRNAs with upstream open reading frames, alternatively spliced isoforms, and selenoprotein mRNAs. ### How does nonsense-mediated mRNA decay work? NMD is triggered during translation when the ribosome terminates at a stop codon that is recognized as premature. In mammals, this recognition is primarily based on the presence of an exon junction complex (EJC) downstream of the stop codon. The EJC recruits UPF2 and UPF3, which interact with UPF1 at the terminating ribosome. This interaction leads to the phosphorylation of UPF1 by SMG1 kinase, which in turn recruits downstream decay factors (SMG5, SMG6, SMG7) that degrade the mRNA. ### What is the meaning of nonsense-mediated mRNA decay? The term "nonsense" refers to the type of mutation that creates a premature stop codon—a "nonsense mutation." "Mediated" indicates that the decay is an active, regulated process involving specific protein factors. "mRNA decay" refers to the degradation of the messenger RNA molecule. Together, the term describes the process by which mRNAs with premature stop codons are selectively degraded. ### What are the key proteins involved in NMD? The core NMD machinery includes: - **UPF1:** The central regulator, an ATP-dependent RNA helicase that is phosphorylated to activate NMD. - **UPF2:** A bridging protein that connects UPF1 to the EJC. - **UPF3 (UPF3A and UPF3B):** EJC-associated proteins that recruit UPF2 to the complex. - **SMG1:** A PI3K-related kinase that phosphorylates UPF1. - **SMG5, SMG6, and SMG7:** Downstream effectors that promote mRNA degradation; SMG6 is an endonuclease, while SMG5 and SMG7 recruit deadenylases and decapping enzymes. - **eRF1 and eRF3:** Translation release factors that recognize the stop codon and recruit UPF1. ### How is NMD related to genetic diseases? Approximately one-third of inherited genetic disorders are caused by nonsense or frameshift mutations that generate PTCs. NMD determines the fate of these mutant transcripts: if the transcript is degraded, the result is a loss-of-function phenotype (haploinsufficiency); if the transcript escapes NMD, a truncated protein is produced, which may have partial function or dominant-negative effects. The efficiency of NMD therefore influences disease severity and is a target for therapeutic intervention. ## Key Takeaways - NMD is a translation-dependent surveillance pathway that degrades mRNAs with premature termination codons, preventing the synthesis of truncated proteins. - In mammals, PTC recognition is primarily based on the presence of an exon junction complex downstream of the stop codon, though EJC-independent mechanisms also exist. - The core NMD machinery includes UPF1, UPF2, UPF3, and the SMG proteins; UPF1 phosphorylation by SMG1 is the committed step in NMD activation. - mRNA degradation in NMD occurs through SMG6-mediated endonucleolytic cleavage and/or SMG5/7-mediated exonucleolytic decay following deadenylation and decapping. - NMD regulates 5–10% of the transcriptome and is itself regulated by autoregulatory loops, developmental cues, and stress responses. - NMD plays a dual role in genetic disease: it protects cells from toxic truncated proteins but can also eliminate mRNAs that would produce partially functional proteins. - Understanding NMD is essential for developing therapeutic strategies, including NMD inhibitors for diseases like cystic fibrosis and Duchenne muscular dystrophy. ## Further Reading - Carrard J, Lejeune F. *Nonsense-mediated mRNA decay, a simplified view of a complex mechanism*. BMB reports. 2023. [PubMed 38052423](https://doi.org/10.5483/BMBRep.2023-0190) - Kurosaki T, Popp MW, Maquat LE. *Quality and quantity control of gene expression by nonsense-mediated mRNA decay*. Nature reviews. Molecular cell biology. 2019. [PubMed 30992545](https://doi.org/10.1038/s41580-019-0126-2) - Wen J, Brogna S. *Nonsense-mediated mRNA decay*. Biochemical Society transactions. 2008. [PubMed 18481993](https://doi.org/10.1042/BST0360514) - Park E, Maquat LE. *Staufen-mediated mRNA decay*. Wiley interdisciplinary reviews. RNA. 2013. [PubMed 23681777](https://doi.org/10.1002/wrna.1168) - Popp MW, Maquat LE. *Nonsense-mediated mRNA Decay and Cancer*. Current opinion in genetics & development. 2018. [PubMed 29121514](https://doi.org/10.1016/j.gde.2017.10.007) - Huang L, Wilkinson MF. *Regulation of nonsense-mediated mRNA decay*. Wiley interdisciplinary reviews. RNA. 2012. [PubMed 23027648](https://doi.org/10.1002/wrna.1137) ## Related Topics - [Nonsense Mediated RNA Decay](/knowledge/molecular-biology/nonsense-mediated-rna-decay) - [mRNA tRNA](/knowledge/molecular-biology/mrna-trna) - [mRNA Translation](/knowledge/molecular-biology/mrna-translation) - [Chaperone Protein](/knowledge/molecular-biology/chaperone-protein) - [Stop Codon](/knowledge/molecular-biology/stop-codon)
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