Proc Natl Acad Sci U S A
January 2017
RNAs besides tRNA and rRNA contain chemical modifications, including the recently described 5' nicotinamide-adenine dinucleotide (NAD) RNA in bacteria. Whether 5' NAD-RNA exists in eukaryotes remains unknown. We demonstrate that 5' NAD-RNA is found on subsets of nuclear and mitochondrial encoded mRNAs in Saccharomyces cerevisiae NAD-mRNA appears to be produced cotranscriptionally because NAD-RNA is also found on pre-mRNAs, and only on mitochondrial transcripts that are not 5' end processed.
View Article and Find Full Text PDFTrends Biochem Sci
October 2015
Stress granules and P-bodies are conserved assemblies of nontranslating mRNAs in eukaryotic cells that can be related to RNA-protein aggregates found in some neurodegenerative diseases. Herein, we examine how the Hsp70/Hsp40 protein chaperones affected the assembly and disassembly of stress granules and P-bodies in yeast. We observed that Hsp70 and the Ydj1 and Sis1 Hsp40 proteins accumulated in stress granules and defects in these proteins led to decreases in the disassembly and/or clearance of stress granules.
View Article and Find Full Text PDFThe control of mRNA translation and degradation is mediated in part by a set of proteins that can inhibit translation and promote decapping, as well as function in the assembly of cytoplasmic mRNP granules referred to as processing bodies (P-bodies). The conserved enhancer of mRNA decapping 3 (Edc3) protein functions to promote both decapping and P-body assembly. Crystal structures of the YjeF_N domain in hEdc3 identified a putative binding site for a small molecule.
View Article and Find Full Text PDFA dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models.
View Article and Find Full Text PDFA 57-year-old man status post several myocardial infarcts and heart transplantation presented with a slowly growing violaceous plaque on his lateral left knee at the site of prior minor trauma. A biopsy revealed a suppurative dermatitis with associated pseudocarcinomatous epithelial hyperplasia. There were multiple non-pigmented eosinophilic organisms with clear cytoplasmic halos within the infiltrate.
View Article and Find Full Text PDFMicroRNAs (miRNAs) regulate gene expression post-transcriptionally through binding specific sites within the 3' untranslated regions (UTRs) of their target mRNAs. Numerous investigations have documented repressive effects of miRNAs and identified factors required for their activity. However, the precise mechanisms by which miRNAs modulate gene expression are still obscure.
View Article and Find Full Text PDFWe present the design, synthesis, and physical and photophysical characterization of Eu(3+) and Gd(3+) complexes formed with two ligands bearing either one or three fluorene sensitizer units. As a novel sensitizing approach, the oligomer length is used to control the energies of the triplet states of the sensitizer and to mediate the sensitizer to lanthanide energy transfer.
View Article and Find Full Text PDFNicotinic acid is one of the most effective agents for both lowering triglycerides and raising HDL. However, the side effect of cutaneous flushing severely limits patient compliance. As nicotinic acid stimulates the GPCR GPR109A and Gi/Go proteins, here we dissected the roles of G proteins and the adaptor proteins, beta-arrestins, in nicotinic acid-induced signaling and physiological responses.
View Article and Find Full Text PDFEnhancement of eukaryotic messenger RNA (mRNA) translation initiation by the 3' poly(A) tail is mediated through interaction of poly(A)-binding protein with eukaryotic initiation factor (eIF) 4G, bridging the 5' terminal cap structure. In contrast to cellular mRNA, translation of the uncapped, non-polyadenylated hepatitis C virus (HCV) genome occurs independently of eIF4G and a role for 3'-untranslated sequences in modifying HCV gene expression is controversial. Utilizing cell-based and in vitro translation assays, we show that the HCV 3'-untranslated region (UTR) or a 3' poly(A) tract of sufficient length interchangeably stimulate translation dependent upon the HCV internal ribosomal entry site (IRES).
View Article and Find Full Text PDFAdeno-associated virus serotype 5 (AAV5) requires sialic acid on host cells to bind and infect. Other parvoviruses, including Aleutian mink disease parvovirus (ADV), canine parvovirus (CPV), minute virus of mice, and bovine parvovirus, also bind sialic acid. Hence, structural homology may explain this functional homology.
View Article and Find Full Text PDFAdenovirus binds its receptor (CAR), enters cells, and replicates. It must then escape to the environment to infect a new host. We found that following infection, human airway epithelia first released adenovirus to the basolateral surface.
View Article and Find Full Text PDFAdeno-associated virus (AAV) is a promising vector for gene transfer in cystic fibrosis. AAV4 and AAV5 both bind to the apical surface of differentiated human airway epithelia, but only AAV5 infects. Both AAV4 and AAV5 require 2,3-linked sialic acid for binding.
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