From: Control of gene expression through the nonsense-mediated RNA decay pathway
Cellular/molecular processes | NMD function and regulation | Target genes | References |
---|---|---|---|
Suppression of aberrant transcripts and transcriptional “noise” | Targets mis-spliced or aberrantly transcribed RNAs, and those derived from mutant genes, transposons and retroviral DNA, for degradation | Many | |
Lymphocyte development | Suppresses expression of unproductive rearrangements of immunoglobulin and Tcell receptor genes | Immunoglobulin, T-cell receptors | |
Embryonic stem cell differentiation | Promotes differentiation by regulating c-myc and the TGFβ/BMP pathways | C-Myc, Smad7 | |
Neurogenesis | Facilitates expression of neuron-specific NMD targets in differentiating neuronal stem cells through miR-128-mediated downregulation of NMD | Many (e.g. Enpp2, Apoe, Abca1, Atp1a2, Kcnj10, Kcnd2, Ttyh1, Ppp2rb2, Stat3, Smad5, Chrdl1, Myt1, Pla2g7, Cercam, Dmd, Slc6a13) | [90] |
Myogenesis | Facilitates expression of the NMD target myogenin because increased SMD activity leads to reduced NMD function | Myogenin | [112] |
Cellular viability | Suppresses expression of GADD45α, leading to inhibition of apoptosis | GADD45α | [140] |
lncRNA regulation | May influence micropeptide expression from a subset of lncRNA transcripts | ~17% of lncRNAs | |
Granulocyte differentiation | Suppresses expression of genes that control granulocyte differentiation and morphology | Dozens (e.g. Lmnb1) | [98] |
Axon guidance | Guides axon migration by limiting the expression of Robo3.2 in commissural neurons | Robo3.2 | [109] |
Synaptic regulation | Impacts the expression of synaptic genes regulated by the RNA-binding protein NOVA, which is itself regulated by synaptic activity | Many (e.g. Dlg3, Dzip1, Ahi1, Slc4a3, Slc4a10, Rasgrf1, Act16b, Scn9a, Stx2, Cdk5rap2, Stxbp2, Plekha5, Lrrcc1) | [110] |
Response to viral infection | Targets viral RNAs to reduce viral load, but also downregulated by specific RNA elements or protein products (e.g. Tax and Rex) to protect viral RNAs | Gag in RSV, HTLV-1 RNAs | |
Stress response (e.g. amino acid deprivation, hypoxia, ER stress) | Upregulates stress response genes as a consequence of downregulation of NMD activity by eIF2α phosphorylation | Many (e.g. ATF4, ATF3, CHOP, IRE1α) | |
Response to chemotherapeutics | Upregulates pro-apoptotic NMD target genes, as a consequence of UPF1 cleavage by caspases during early stages of apoptosis that downregulates NMD | GADD45α, GADD45β, BAK1, GAS5, DAP3, DUSP2 |