title: Screening of posttranscriptional regulatory molecules of IκB-ζ.
abstract: Posttranscriptional regulatory elements in the 3'-untranslated region (UTR) of mRNAs play an important role in mRNA stabilization. Induction of IκB-ζ, a critical transcriptional regulator in the innate immune response, is mediated via specific mRNA stabilization by lipopolysaccharide (LPS) and interleukin (IL)-1β. It is known that the 3'-UTR of IκB-ζ, especially 165 nucleotides after the stop codon, plays a crucial role in mRNA stability. Herein, we show that AU-rich elements and miRNA targets in these 165 3'-UTR nucleotides are dispensable for stability of IκB-ζ mRNA. Additionally, NF-κB activation is important for IκB-ζ transcription, but dispensable for IκB-ζ mRNA stability. Interestingly, high-throughput screening results show that MyD88, a signal molecule responsive to LPS/IL-1β stimulation, is key for stabilizing IκB-ζ mRNA expression. Moreover, MyD88-deficient macrophages exhibited a decreased half-life of IκB-ζ mRNA expression. These results indicate that the LPS/IL-1β-MyD88 axis plays a crucial role for stabilization of IκB-ζ mRNA.
authors.affiliation: Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, 6-3, Aramaki, Aoba, Sendai, Miyagi 980-8578, Japan; School of Medicine, Gifu University, 1-1, Yanagido, Gifu 501-1194, Japan. Electronic address: ta-maru@umin.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: MaruYama
authors.affiliation: Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, 6-3, Aramaki, Aoba, Sendai, Miyagi 980-8578, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Sayama
authors.affiliation: Laboratory of Vaccine Science, Immunology Frontier Research Center, World Premier Institute, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.affiliation: Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, 6-3, Aramaki, Aoba, Sendai, Miyagi 980-8578, Japan.
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Muta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D000067996:RAW 264.7 Cells; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins; D010446:Peptide Fragments; C052994:interleukin-1beta (163-171)
keywords: 3′-UTR; IκB-ζ; MyD88; Posttranscriptional regulation