Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 17 January 2020 / Approved: 18 January 2020 / Online: 18 January 2020 (10:21:18 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2020, 21, 1335
DOI: 10.3390/ijms21041335

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 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. Therefore, these RNA quality control processes eliminate abnormal PTC-containing mRNAs from the cells by using positive and negative responses. In this review, we will describe the general mechanisms of NMD and NAS and their respective involvement in the decay of aberrant immunoglobulin and TCR transcripts in lymphoid cells.

Subject Areas

immunoglobulin (Ig); nonsense-mediated mRNA decay (NMD); nonsense-associated altered splicing (NAS); B lymphocytes; plasma cells

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