In mammalian cells, nonsense-mediated mRNA decay (NMD) is a consequence of nonsense codon recognition during a pioneer round of translation. This round can occur largely before or largely after the release of newly synthesized mRNA from nuclei, depending on the mRNA, and likely utilizes cytoplasmic ribosomes. We show that increasing the cellular concentration of the splicing factor SF2/ASF augm...

Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance pathway that recognizes and degrades aberrant mRNAs containing premature stop codons. A critical protein in NMD is Upf1p, which belongs to the helicase super family 1 (SF1), and is thought to utilize the energy of ATP hydrolysis to promote transitions in the structure of RNA or RNA-protein complexes. The crystal structure of the catalyt...

Clf1 is a conserved spliceosome assembly factor composed predominately of TPR repeats. Here we show that the TPR elements are not functionally equivalent, with the amino terminus of Clf1 being especially sensitive to change. Deletion and add-back experiments reveal that the splicing defect associated with TPR removal results from the loss of TPR-specific sequence information. Twelve mutants wer...

Promoter methylation is one of the main epigenetic mechanisms that lead to the inactivation of tumor suppressor genes during carcinogenesis. Due to the reversible nature of DNA methylation, many studies have been performed to correct theses epigenetic defects by inhibiting DNA methyltransferases (DNMTs). In this case novel therapeutics especially siRNA oligonucleotides have been used to specifi...

Nonsense-mediated mRNA decay (NMD) generally involves nonsense codon recognition by translating ribosomes at a position approximately 25 nts upstream of a splicing-generated exon junction complex of proteins. As such, NMD provides a means to degrade abnormal mRNAs that encode potentially deleterious truncated proteins. Additionally, an estimated one-third of naturally occurring, alternatively s...

The Nonsense-Mediated mRNA Decay (NMD) pathway mediates the rapid degradation of mRNAs that contain premature stop mutations in eukaryotic organisms. It was recently shown that mutations in three yeast genes that encode proteins involved in the NMD process, UPF1, UPF2, and UPF3, also reduce the efficiency of translation termination. In the current study, we compared the efficiency of translatio...

Summary Type I interferons (IFNs) are critical cytokines in the host defense against invading pathogens. Sustained production of IFNs, however, is detrimental to host, as it provokes autoimmune diseases. Thus, expression IFNs tightly controlled. We report that mRNA 5′ cap-binding protein 4EHP plays a key role regulating type IFN concomitant with controlling virus replication, both i...

Hypertrophic cardiomyopathy (HCM), characterized by asymmetric left ventricular hypertrophy, can lead to severe arrhythmias and sudden cardiac death. The mechanism underlying hypertrophy in HCM has not been fully elucidated. We recently showed that the messenger RNA (mRNA) transcriptome derived from myectomy tissue is gene expression reprogramming predominant transcriptional down-regulation of ...