Translational control of the interferon regulatory factor 2 mRNA by IRES element.
Translational control represents an important mode of regulation of gene expression under stress conditions. We have studied the translation of interferon regulatory factor 2 (IRF2) mRNA, a negative regulator of transcription of interferon-stimulated genes and demonstrated the presence of internal ribosome entry site (IRES) element in the 5'UTR of IRF2 RNA. Various control experiments ruled out the contribution of leaky scanning, cryptic promoter activity or RNA splicing in the internal initiation of IRF2 RNA. It seems IRF2-IRES function is not sensitive to eIF4G cleavage, since its activity was only marginally affected in presence of Coxsackievirus 2A protease. Interferon alpha treatment did not affect the IRF2-IRES activity or the protein level significantly. Also, in cells treated with tunicamycin [an agent causing endoplasmic reticulum (ER) stress], the IRF2-IRES activity and the protein levels were unaffected, although the cap-dependent translation was severely impaired. Analysis of the cellular protein binding with the IRF2-IRES suggests certain cellular factors, which might influence its function under stress conditions. Interestingly, partial knockdown of PTB protein significantly inhibited the IRF2-IRES function. Taken together, it appears that IRF2 gene expression during stress condition is controlled by the IRES element, which in turn influences the cellular response.
Dhar
Debojyoti
D
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore-560012, India.
Roy
Swagata
S
Das
Saumitra
S
D020121:5' Untranslated Regions / Q000737:chemistry*; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D050836:Interferon Regulatory Factor-2 / Q000235:genetics*; D016898:Interferon-alpha / Q000494:pharmacology; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D011401:Promoter Regions, Genetic; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D012270:Ribosomes / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
D020121:5' Untranslated Regions; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D016898:Interferon-alpha; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D014415:Tunicamycin
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