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Mechanisms and Regulation of Nonsense-Mediated mRNA Decay and Nonsense-Associated Altered Splicing in Lymphocytes

Unit CNRS 7276 - INSERM U1262—Limoges University, 2 rue du Docteur Marcland, 87025 Limoges, France
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Author to whom correspondence should be addressed.
Present address: Segal Cancer Center, Lady Davis Institute for Medical Research and Departments of Oncology and Medicine, McGill University, Montréal, QC H3T 1E2, Canada.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(4), 1335; https://doi.org/10.3390/ijms21041335
Received: 17 January 2020 / Revised: 12 February 2020 / Accepted: 13 February 2020 / Published: 17 February 2020
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. View Full-Text
Keywords: Immunoglobulin (Ig); nonsense-mediated mRNA decay (NMD); nonsense-associated altered splicing (NAS); B lymphocytes; plasma cells Immunoglobulin (Ig); nonsense-mediated mRNA decay (NMD); nonsense-associated altered splicing (NAS); B lymphocytes; plasma cells
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Lambert, J.-M.; Ashi, M.O.; Srour, N.; Delpy, L.; Saulière, J. Mechanisms and Regulation of Nonsense-Mediated mRNA Decay and Nonsense-Associated Altered Splicing in Lymphocytes. Int. J. Mol. Sci. 2020, 21, 1335.

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