Nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that selectively degrades mRNAs harboring premature termination (nonsense) codons. If translated, these mRNAs can produce truncated proteins with dominant-negative or deleterious gain-of-function activities. In this review, we describe the molecular mechanism of NMD. We first cover conserved factors known to be involved in NMD in all eukaryotes. We then describe a unique protein complex that is deposited on mammalian mRNAs during splicing, which defines a stop codon as premature. Interaction between this exon-junction complex (EJC) and NMD factors assembled at the upstream stop codon triggers a series of steps that ultimately lead to mRNA decay. We discuss whether these proofreading events preferentially occur during a "pioneer" round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC.
NAM7 nuclear gene encodes a novel member of a family of helicases with a Zn-ligand motif and is involved in mitochondrial functions in Saccharomyces cerevisiae
The product of the yeast UPF1 gene is required for rapid turnover of mRNAs containing a premature translational termination codon
Identification and characterization of genes that are required for the accelerated degradation of mRNAs containing a premature translational termination codon
Nuclear degradation of nonsense mutated beta-globin mRNA: a post-transcriptional mechanism to protect heterozygotes from severe clinical manifestations of beta-thalassemia?
Nonsense but not missense mutations can decrease the abundance of nuclear mRNA for the mouse major urinary protein, while both types of mutations can facilitate exon skipping.
A nuclear cap-binding complex binds Balbiani ring pre-mRNA cotranscriptionally and accompanies the ribonucleoprotein particle during nuclear export
Genetic and biochemical characterization of mutations in the ATPase and helicase regions of the Upf1 protein.
Identification and characterization of mutations in the UPF1 gene that affect nonsense suppression and the formation of the Upf protein complex but not mRNA turnover.
Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated mRNA decay pathway.
Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein
Identifying the right stop: determining how the surveillance complex recognizes and degrades an aberrant mRNA
The surveillance complex interacts with the translation release factors to enhance termination and degrade aberrant mRNAs
A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance
Intron function in the nonsense-mediated decay of beta-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm
RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancer
mRNA surveillance in eukaryotes: kinetic proofreading of proper translation termination as assessed by mRNP domain organization?
SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast.
REF, an evolutionary conserved family of hnRNP-like proteins, interacts with TAP/Mex67p and participates in mRNA nuclear export
Characterization of the biochemical properties of the human Upf1 gene product that is involved in nonsense-mediated mRNA decay
Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes.
Identification and characterization of human orthologues to Saccharomyces cerevisiae Upf2 protein and Upf3 protein (Caenorhabditis elegans SMG-4)
Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability
Splicing and 3' end formation in the definition of nonsense-mediated decay-competent human beta-globin mRNPs
Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon
The role of Upf proteins in modulating the translation read-through of nonsense-containing transcripts
Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements.
Identification of two novel inactive DFR-A alleles responsible for failure to produce anthocyanin and development of a simple PCR-based molecular marker for bulb color selection in onion (Allium cepa L.)
Alternative splicing of transcription factors in plant responses to low temperature stress: mechanisms and functions.
Transcripts of the nicotinic acetylcholine receptor subunit gene Pxylα6 with premature stop codons are associated with spinosad resistance in diamondback moth, Plutella xylostella
Genetic analysis in a patient presenting with meningioma and familial isolated pituitary adenoma (FIPA) reveals selective involvement of the R81X mutation of the AIP gene in the pathogenesis of the pituitary tumor
Chlorophyll-deficient mutants of Chlamydomonas reinhardtii that accumulate magnesium protoporphyrin IX.
Linkage mapping, molecular cloning and functional analysis of soybean gene Fg2 encoding flavonol 3-O-glucoside (1 → 6) rhamnosyltransferase
Mutations of the UPF3B gene, which encodes a protein widely expressed in neurons, are associated with nonspecific mental retardation with or without autism
Visualization and genetic analysis of alternative splicing regulation in vivo using fluorescence reporters in transgenic Caenorhabditis elegans
Dual roles of the nuclear cap-binding complex and SERRATE in pre-mRNA splicing and microRNA processing in Arabidopsis thaliana
Characterization of arrangement and expression of the T cell receptor gamma locus in the sandbar shark
Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection
Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator
Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex
A Drosophila behavioral mutant, down and out (dao), is defective in an essential regulator of Erg potassium channels
rnaset2 mutant zebrafish model familial cystic leukoencephalopathy and reveal a role for RNase T2 in degrading ribosomal RNA
Major source of antigenic peptides for the MHC class I pathway is produced during the pioneer round of mRNA translation
Spontaneous mutation of the Dock2 gene in Irf5-/- mice complicates interpretation of type I interferon production and antibody responses
Loss of deeply conserved C-class floral homeotic gene function and C- and E-class protein interaction in a double-flowered ranunculid mutant
Inhibition of SMG-8, a subunit of SMG-1 kinase, ameliorates nonsense-mediated mRNA decay-exacerbated mutant phenotypes without cytotoxicity
Translation of pre-spliced RNAs in the nuclear compartment generates peptides for the MHC class I pathway
Inhibition of nonsense-mediated mRNA decay by the natural product pateamine A through eukaryotic initiation factor 4AIII
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis