Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The multiprotein exon junction complex (EJC) is assembled on mRNAs as a consequence of splicing. EJC core components maintain a stable grip on mRNAs even as the overall EJC protein composition evolves while mRNAs travel to the cytoplasm. Here we show that recombinant EJC subunits MLN51, MAGOH and Y14, together with the DEAD-box protein eIF4AIII bound to ATP, are necessary and sufficient to form a highly stable complex on single-stranded RNA. Cross-linking and RNase protection studies indicate that this recombinant complex recapitulates the EJC core. The stable association of the recombinant EJC core with RNA is maintained by inhibition of eIF4AIII ATPase activity by MAGOH-Y14. We elucidate the modalities of EJC binding to RNA and provide the first example of how cellular machineries may use RNA helicases to clamp several proteins onto RNA in stable and sequence-independent manners.
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PMID:The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. 1617 Mar 25

Ribonucleoprotein complexes (RNP) remodeling by DEAD-box proteins is required at all stages of cellular RNA metabolism. These proteins are composed of a core helicase domain lacking sequence specificity; flanking protein sequences or accessory proteins target and affect the core's activity. Here we examined the interaction of eukaryotic initiation factor 4AI (eIF4AI), the founding member of the DEAD-box family, with two accessory factors, eIF4B and eIF4H. We find that eIF4AI forms a stable complex with RNA in the presence of AMPPNP and that eIF4B or eIF4H can add to this complex, also dependent on AMPPNP. For both accessory factors, the minimal stable complex with eIF4AI appears to have 1:1 protein stoichiometry. However, because eIF4B and eIF4H share a common binding site on eIF4AI, their interactions are mutually exclusive. The eIF4AI:eIF4B and eIF4AI:eIF4H complexes have the same RNase resistant footprint as does eIF4AI alone (9-10 nucleotides [nt]). In contrast, in a selective RNA binding experiment, eIF4AI in complex with either eIF4B or eIF4H preferentially bound RNAs much longer than those bound by eIF4AI alone (30-33 versus 17 nt, respectively). The differences between the RNase resistant footprints and the preferred RNA binding site sizes are discussed, and a model is proposed in which eIF4B and eIF4H contribute to RNA affinity of the complex through weak interactions not detectable in structural assays. Our findings mirror and expand on recent biochemical and structural data regarding the interaction of eIF4AI's close relative eIF4AIII with its accessory protein MLN51.
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PMID:Interactions between eIF4AI and its accessory factors eIF4B and eIF4H. 1871 48

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with high invasion and metastasis capacities. Circular RNAs (circRNAs) were evidenced to take part in the progression of multifarious cancers, including HCC. However, the role of circ_0091579 in HCC progression has not been fully described. This study aimed to explore the function of circ_0091579 and its potential regulatory mechanism in the progression of HCC. Materials and Methods: The expression of circ_0091579, microRNA-490-5p (miR-490-5p), and cancer susceptibility candidate 3 (CASC3) in HCC tissues and cells was detected by quantitative real-time polymerase chain reaction. The circular characteristic and stability of circ_0091579 were verified by RNase R digestion and actinomycin D reaction assays. Cell proliferation, migration, and invasion were determined by methyl thiazolyl tetrazolium assay and Transwell assay, respectively. The level of glycolysis was evaluated by glucose consumption and lactate production. The levels of proteins were examined by Western blot. The interaction between miR-490-5p and circ_0091579 or CASC3 was certified by Dual-luciferase reporter assay. Results: circ_0091579 and CASC3 were upregulated, while miR-490-5p was downregulated in HCC tissues and cells. Silencing of either circ_0091579 or CASC3 suppressed cell proliferation, migration, invasion, and glycolysis in HCC cells. Moreover, miR-490-5p was verified to directly bind to circ_0091579 and CASC3. Circ_0091579 upregulated CASC3 by sponging miR-490-5p in HCC cells to promote cell proliferation, invasion, and migration. Conclusion: circ_0091579 promoted cell proliferation, migration, invasion, and glycolysis partially through miR-490-5p/CASC3 axis in HCC cells.
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PMID:Circular RNA circ_0091579 Promotes Hepatocellular Carcinoma Proliferation, Migration, Invasion, and Glycolysis Through miR-490-5p/CASC3 Axis. 3267 66