15 research outputs found
The eEF1Îł Subunit Contacts RNA Polymerase II and Binds Vimentin Promoter Region
Here, we show that the eukaryotic translation elongation factor 1 gamma (eEF1Îł) physically interacts with the RNA polymerase II (pol II) core subunit 3 (RPB3), both in isolation and in the context of the holo-enzyme. Importantly, eEF1Îł has been recently shown to bind Vimentin mRNA. By chromatin immunoprecipitation experiments, we demonstrate, for the first time, that eEF1Îł is also physically present on the genomic locus corresponding to the promoter region of human Vimentin gene. The eEF1Îł depletion causes the Vimentin protein to be incorrectly compartmentalised and to severely compromise cellular shape and mitochondria localisation. We demonstrate that eEF1Îł partially colocalises with the mitochondrial marker Tom20 and that eEF1Îł depletion increases mitochondrial superoxide generation as well as the total levels of carbonylated proteins. Finally, we hypothesise that eEF1Îł, in addition to its role in translation elongation complex, is involved in regulating Vimentin gene by contacting both pol II and the Vimentin promoter region and then shuttling/nursing the Vimentin mRNA from its gene locus to its appropriate cellular compartment for translation
Epigenetic Activation of a Subset of mRNAs by eIF4E Explains Its Effects on Cell Proliferation
BACKGROUND: Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5′ cap-binding protein, plays a major role in translational control. To understand how eIF4E affects cell proliferation and survival, we studied mRNA targets that are translationally responsive to eIF4E. METHODOLOGY/PRINCIPAL FINDINGS: Microarray analysis of polysomal mRNA from an eIF4E-inducible NIH 3T3 cell line was performed. Inducible expression of eIF4E resulted in increased translation of defined sets of mRNAs. Many of the mRNAs are novel targets, including those that encode large- and small-subunit ribosomal proteins and cell growth-related factors. In addition, there was augmented translation of mRNAs encoding anti-apoptotic proteins, which conferred resistance to endoplasmic reticulum-mediated apoptosis. CONCLUSIONS/SIGNIFICANCE: Our results shed new light on the mechanisms by which eIF4E prevents apoptosis and transforms cells. Downregulation of eIF4E and its downstream targets is a potential therapeutic option for the development of novel anti-cancer drugs
Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression
Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration
Evolution of the EF-Tu Family
Two recent developments have allowed for the identification of a “family” of EF-Tu-like proteins. The first is the biochemical characterization of several proteins which bind aminoacyl-tRNAs in a GTP-dependent manner. The second has been the identification of sequence identity elements that are similar to EF-Tu and many of which would allow for a similar three dimensional structure. A key element in this second part has been the emergence of a 2.6 Å resolution crystal structure for Escherichia coli EF-Tu (Kjeldgaard and Nyborg, 1992). This report discusses the evolution of prokaryotic EF-Tu into its eukaryotic counterpart EF-la as well as the evolution of EF-Tu into proteins with distinct, but related functional properties. While not all of the family members have been characterized biochemically, based upon their similarity to EF-Tu and the presence of the three GTP consensus elements, it is likely that all the family members function by binding aminoacyl-tRNA in a GTP-dependent manner