Journal Article

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

Srour, Nivine, Lambert, Jean-Marie, Delpy, Laurent, Saulière, Jérôme, Ashi, Mohamad Omar

2020

Overview

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.

• Publisher: MDPI
• Subject: Alternative Splicing / B-Lymphocytes - metabolism / Cell Differentiation / Codon, Nonsense - genetics / Codon, Nonsense - metabolism / Frameshift Mutation / Gain of Function Mutation / Nonsense Mediated mRNA Decay / Plasma Cells - metabolism / Receptors, Antigen, T-Cell - genetics / Receptors, Antigen, T-Cell - metabolism / Review / RNA Stability / Up-Regulation