Post-transcriptional Regulation of Genes Encoding Anti-microbial Peptides in Drosophila
pmid: 19176529
pmc: PMC2659254
Post-transcriptional Regulation of Genes Encoding Anti-microbial Peptides in Drosophila
Secretion of antimicrobial peptides (AMPep) is a central defense mechanism used by invertebrates to combat infections. In Drosophila the synthesis of these peptides is a highly regulated process allowing their rapid release in the hemolymph upon contact with pathogens and the arrest of their production after pathogen clearance. We observed that AMPep genes have either a transient or sustained expression profile in S2 Drosophila cells treated with peptidoglycan. Moreover, AMPep genes containing AU-rich elements (ARE) in their 3'-untranslated region (UTR) are subject to a post-transcriptional control affecting mRNA stability, thereby contributing to their transient expression profile. Cecropin A1 (CecA1) constitutes the prototype of this latter class of AMPeps. CecA1 mRNA bears in its 3'-UTR an ARE similar to class II AREs found in several short-lived mammalian mRNAs. In response to immune deficiency cascade signaling activated by Gram-negative peptidoglycans, CecA1 mRNA is transiently stabilized and subsequently submitted to deadenylation and decay mediated by the ARE present in its 3'-UTR. The functionality of CecA1 ARE relies on its ability to recruit TIS11 protein, which accelerates CecA1 mRNA deadenylation and decay. Moreover, we observed that CecA1 mRNA deadenylation is a biphasic process. Whereas early deadenylation is independent of TIS11, the later deadenylation phase depends on TIS11 and is mediated by CAF1 deadenylase. We also report that in contrast to tristetraprolin, its mammalian homolog, TIS11, is constitutively expressed in S2 cells and accumulates in cytoplasmic foci distinct from processing bodies, suggesting that the Drosophila ARE-mediated mRNA deadenylation and decay mechanism is markedly different in invertebrates and mammals.
- Université Libre de Bruxelles Belgium
3' Untranslated Regions -- genetics, RNA Stability -- drug effects, Transcription, Genetic, Chromosomal Proteins, Non-Histone, RNA Stability, Antimicrobial Cationic Peptides -- biosynthesis, Drosophila Proteins -- metabolism, Peptidoglycan, RNA Stability -- physiology, Signal Transduction -- drug effects, Tristetraprolin -- metabolism, Molecular Chaperones -- genetics, 3' Untranslated Regions -- metabolism, Peptidoglycan -- pharmacology, Non-Histone -- genetics, Cell Line, Tristetraprolin, Gram-Negative Bacteria, Animals, Drosophila Proteins, Signal Transduction -- physiology, Gram-Negative Bacteria -- chemistry, RNA-Binding Proteins -- genetics, 3' Untranslated Regions, Chromosomal Proteins, Non-Histone -- metabolism, Chromosomal Proteins, Non-Histone -- genetics, RNA-Binding Proteins, Non-Histone -- metabolism, Antimicrobial Cationic Peptides -- genetics, Drosophila Proteins -- genetics, Sciences bio-médicales et agricoles, RNA-Binding Proteins -- metabolism, Molecular Chaperones -- metabolism, Chromosomal Proteins, Genetic -- physiology, Transcription, Genetic -- physiology, Drosophila melanogaster, Peptidoglycan -- chemistry, Retinoblastoma-Binding Protein 4, Tristetraprolin -- genetics, Transcription, Antimicrobial Cationic Peptides, Molecular Chaperones, Signal Transduction
3' Untranslated Regions -- genetics, RNA Stability -- drug effects, Transcription, Genetic, Chromosomal Proteins, Non-Histone, RNA Stability, Antimicrobial Cationic Peptides -- biosynthesis, Drosophila Proteins -- metabolism, Peptidoglycan, RNA Stability -- physiology, Signal Transduction -- drug effects, Tristetraprolin -- metabolism, Molecular Chaperones -- genetics, 3' Untranslated Regions -- metabolism, Peptidoglycan -- pharmacology, Non-Histone -- genetics, Cell Line, Tristetraprolin, Gram-Negative Bacteria, Animals, Drosophila Proteins, Signal Transduction -- physiology, Gram-Negative Bacteria -- chemistry, RNA-Binding Proteins -- genetics, 3' Untranslated Regions, Chromosomal Proteins, Non-Histone -- metabolism, Chromosomal Proteins, Non-Histone -- genetics, RNA-Binding Proteins, Non-Histone -- metabolism, Antimicrobial Cationic Peptides -- genetics, Drosophila Proteins -- genetics, Sciences bio-médicales et agricoles, RNA-Binding Proteins -- metabolism, Molecular Chaperones -- metabolism, Chromosomal Proteins, Genetic -- physiology, Transcription, Genetic -- physiology, Drosophila melanogaster, Peptidoglycan -- chemistry, Retinoblastoma-Binding Protein 4, Tristetraprolin -- genetics, Transcription, Antimicrobial Cationic Peptides, Molecular Chaperones, Signal Transduction
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