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MIMI_L496: Putative mRNA cap-binding protein IF4E

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Cap in hand Targeting eIF4E. Enzymatic Synthesis of RNAs Capped with Nucleotide Analogues Reveals the Molecular Basis for Substrate Selectivity of RNA Capping Enzyme: Impacts on RNA Metabolism. Abstract RNA cap binding proteins have evolved to specifically bind to the N7-methyl guanosine cap structure found at the 5’ ends of eukaryotic mRNAs.

Enzymatic Synthesis of RNAs Capped with Nucleotide Analogues Reveals the Molecular Basis for Substrate Selectivity of RNA Capping Enzyme: Impacts on RNA Metabolism

The specificity of RNA capping enzymes towards GTP for the synthesis of this structure is therefore crucial for mRNA metabolism. The fact that ribavirin triphosphate was described as a substrate of a viral RNA capping enzyme, raised the possibility that RNAs capped with nucleotide analogues could be generated in cellulo. Owing to the fact that this prospect potentially has wide pharmacological implications, we decided to investigate whether the active site of the model Paramecium bursaria Chlorella virus-1 RNA capping enzyme was flexible enough to accommodate various purine analogues. Using this approach, we identified several key structural determinants at each step of the RNA capping reaction and generated RNAs harboring various different cap analogues. Editor: André Paul Gerber, University of Surrey, United Kingdom Introduction Methods.

Characterization of a mimivirus RNA cap guanine-N2 methyltransferase. + Author Affiliations Abstract A 2,2,7-trimethylguanosine (TMG) cap is a signature feature of eukaryal snRNAs, telomerase RNAs, and trans-spliced nematode mRNAs.

Characterization of a mimivirus RNA cap guanine-N2 methyltransferase

MIMI_L496 - Eukaryotic translation initiation factor 4E homolog - Acanthamoeba polyphaga mimivirus (APMV) - MIMI_L496 gene & protein. Select a section on the left to see content.

MIMI_L496 - Eukaryotic translation initiation factor 4E homolog - Acanthamoeba polyphaga mimivirus (APMV) - MIMI_L496 gene & protein

<p>Provides any useful information about the protein, mostly biological knowledge. </p><p><a href='.. /manual/function_section' target='_top'>More... </a></p>Functioni Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures.

Past IF4E crystallizations & purifications

eIF4E Binding Protein 1 (4E-BP1) Combination of Trp and Glu residues for recognition of mRNA cap structure Analysis of m7G base recognition site of human cap binding protein (IF-4E) by site-directed mutagenesis - Ueda - 2001 - FEBS Letters. Von der Haar et al 2004. * 133440 - EUKARYOTIC TRANSLATION INITIATION FACTOR 4E; EIF4E. Pause et al. (1994) identified 2 homologous proteins, EIF4EBP1 (602223) and EIF4EBP2 (602224), that bind to EIF4E and may regulate its activity.

* 133440 - EUKARYOTIC TRANSLATION INITIATION FACTOR 4E; EIF4E

Jones et al. (1997) stated that EIF4E is the rate-limiting component in protein synthesis and may play a role in growth regulation. The overexpression of EIF4E can cause malignant transformation. Waskiewicz et al. (1997) identified EIF4E as a potential physiologic substrate for Mnk1 (MKNK1; 606724) and Mnk2 (MKNK2; 605069) in mouse. Using coimmunoprecipitation experiments, Pyronnet et al. (1999) demonstrated that MNK1 interacts with the EIF4F complex via its interaction with the C-terminal region of EIF4G, not through a direct interaction with EIF4E. An EIF4E mutant lacking EIF4G-binding capability was poorly phosphorylated in cells. In mammals, MTOR (601231) cooperates with PI3K (see 171834)-dependent effectors in a biochemical signaling pathway to regulate the size of proliferating cells.

PNAS 1990 De Benedetti 8212 6. Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Author Affiliations Edited by Peter K.

Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap

Vogt, The Scripps Research Institute, La Jolla, CA, and approved November 8, 2004 (received for review September 17, 2004) Abstract The eukaryotic translation initiation factor eIF4E is deregulated in many human cancers, and its overexpression in cells leads to malignant transformation. Oncogenic properties of eIF4E are directly linked to its ability to bind 7-methyl guanosine of the 5′ mRNA. Whereas the precise causes of neoplasia and malignancy are known only for a few human cancers, deregulated tumor suppressors and oncogenes that maintain and enhance the malignant phenotype are becoming relatively well described (1, 2). eIF4E is overexpressed in a wide variety of malignant cell lines and primary human tumors such as carcinomas of the breast (5), colon (6), and head and neck (7), non-Hodgkin's lymphomas (8), and chronic and acute M4/M5 myelogenous leukemias (9).

Methods Results and Discussion Fig. 1. Fig. 2. Fig. 3. Fig. 4. Conclusions Acknowledgments. Weak binding affinity of human 4EHP for mRNA cap analogs. + Author Affiliations ↵4 These authors contributed equally to this work.

Weak binding affinity of human 4EHP for mRNA cap analogs

Abstract Ribosome recruitment to the majority of eukaryotic mRNAs is facilitated by the interaction of the cap binding protein, eIF4E, with the mRNA 5′ cap structure. eIF4E stimulates translation through its interaction with a scaffolding protein, eIF4G, which helps to recruit the ribosome. Metazoans also contain a homolog of eIF4E, termed 4EHP, which binds the cap structure, but not eIF4G, and thus cannot stimulate translation, but it instead inhibits the translation of only one known, and possibly subset mRNAs. To understand why 4EHP does not inhibit general translation, we studied the binding affinity of 4EHP for cap analogs using two methods: fluorescence titration and stopped-flow measurements.

All nuclear transcribed eukaryotic mRNAs possess a common structure called a “cap” at their 5′ end, which consists of 7-methylguanosine bound by a 5′-5′-triphosphate bridge to the first transcribed nucleotide. Footnotes.

Viral IF4E moderation strategies