Nonsense-mediated mRNA decay (NMD) is a conserved proofreading mechanism that protects eukaryotic cells from the potentially deleterious effects of truncated proteins. Studies of Saccharomyces cerevisiae imply that NMD is a predominantly cytoplasmic decay pathway, while studies of mammalian systems suggest that decay of most substrate mRNAs may occur while they are still associated with the nuc...

One of the most common splice variations are small exon length variations caused by the use of alternative donor or acceptor splice sites that are in very close proximity on the pre-mRNA. Among these, three-nucleotide variations at so-called NAGNAG tandem acceptor sites have recently attracted considerable attention, and it has been suggested that these variations are regulated and serve to fin...

Neuraminidase type X (NMD-type-X, Sigma Chemical Co., St. Louis, Mo.), which is obtained from a further purification of neuraminidase type V (NMD-type-V, Sigma), markedly enhanced the release of O2- and H2O2 from phagocytosing human polymorphonuclear leukocytes (PMN). In contrast, O2 consumption by NMD-type-X-treated PMN was identical to that of untreated PMN. Morphological observations suggest...

All eukaryotes possess the ability to detect and degrade transcripts harboring premature signals for the termination of translation. Despite the ubiquitous nature of nonsense-mediated mRNA decay (NMD) and its demonstrated role in the modulation of phenotypes resulting from selected nonsense alleles, very little is known regarding its basic mechanism or the selective pressure for complete evolut...

Structural and magnetic properties of laminated sNd,DydsFe,Co,Nb,Bd5.5 /Fe nanocomposites are investigated. Normally, the addition of the soft phase to the hard phase enhances the remanence but deteriorates the permanent-magnet performance of the material by reducing the coercivity. In the present system, the coercivity increases to 1608 kA/m s20.2 kOed in thermally processed Nd–Dy–Fe–Co–Nb–Bs1...

It is widely believed that translation occurs only in the cytoplasm of eukaryotes, but recent results suggest some takes place in nuclei, coupled to transcription. Support for this heterodoxy comes from studies of the nonsense-mediated decay (NMD) pathway; this pathway probably uses ribosomes to proofread messenger RNAs. We find components of the machineries involved in transcription, translati...

Many gene expression factors contain repetitive phosphorylation sites for single kinases, but the functional significance is poorly understood. Here we present evidence for hyperphosphorylation as a mechanism allowing UPF1, the central factor in nonsense-mediated decay (NMD), to increasingly attract downstream machinery with time of residence on target mRNAs. Indeed, slowing NMD by inhibiting l...

NMD (nonsense-mediated mRNA decay) is a cellular quality-control mechanism in which an otherwise stable mRNA is destabilized by the presence of a premature termination codon. We have defined the set of endogenous NMD substrates, demonstrated that they are available for NMD at every round of translation, and showed that premature termination and normal termination are not equivalent biochemical ...

Nonsense-mediated decay (NMD) is a eukaryotic quality control pathway, involving conserved proteins UPF1, UPF2 and UPF3b, which detects and degrades mRNAs with premature stop codons. Human UPF2 comprises three tandem MIF4G domains and a C-terminal UPF1 binding region. MIF4G-3 binds UPF3b, but the specific functions of MIF4G-1 and MIF4G-2 are unknown. Crystal structures show that both MIF4G-1 an...

Meaningfulness of the relevant (MR) and irrelevant (MI) syllables and contiguity of the relevant syllables were manipulated in a task analogous to concept formation. Stimuli consisted of two nonsense syllables with one being relevant, in that it was consistently paired with a number response, and the other being irrelevant, in that it appeared equally often with each number response. MR was var...