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Published on: October 9, 2014
Mechanisms and Regulation of Nonsense-Mediated mRNA Decay and Nonsense-Associated Altered Splicing in Lymphocytes
Jean-Marie Lambert1, Mohamad Omar Ashi1, Nivine Srour1,2
1Unit CNRS 7276 - INSERM U1262 - Limoges University, 2 rue du Docteur Marcland, 87025 Limoges, France.
Abstract:
The presence of premature termination codons (PTCs) in transcripts is dangerous for the cell as they encode potentially deleterious truncated proteins that can act with dominant-negative or gain-of-function effects. To avoid the synthesis of these shortened polypeptides, several RNA surveillance systems can be activated to decrease the level of PTC-containing mRNAs. Nonsense-mediated mRNA decay (NMD) ensures an accelerated degradation of mRNAs harboring PTCs by using several key NMD factors such as up-frameshift (UPF) proteins. Another pathway called nonsense-associated altered splicing (NAS) upregulates transcripts that have skipped disturbing PTCs by alternative splicing. Thus, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphocytes.
Insights
Cells eliminate dangerous truncated proteins using RNA surveillance. Nonsense-mediated mRNA decay (NMD) and nonsense-associated altered splicing (NAS) degrade or correct faulty messenger RNAs (mRNAs) containing premature termination codons (PTCs).
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Premature termination codons (PTCs) create unstable transcripts encoding harmful proteins.
- Cells employ RNA surveillance to prevent the synthesis of truncated proteins.
- Nonsense-mediated mRNA decay (NMD) and nonsense-associated altered splicing (NAS) are key RNA quality control pathways.
Purpose of the Study:
- To review the mechanisms of NMD and NAS.
- To explore the role of NMD and NAS in lymphocyte immunoglobulin and TCR transcript regulation.
Main Methods:
- Literature review of NMD and NAS pathways.
- Analysis of RNA surveillance in lymphocyte gene expression.
Main Results:
- NMD targets PTC-containing mRNAs for degradation.
- NAS promotes alternative splicing to bypass PTCs, upregulating functional transcripts.
- Both pathways protect cells from deleterious truncated proteins.
Conclusions:
- NMD and NAS are crucial RNA quality control systems.
- These pathways eliminate aberrant transcripts, maintaining cellular integrity.
- Understanding NMD and NAS is vital for lymphocyte biology and disease research.
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