RRC ID 54357
Author MaruYama T, Sayama A, Ishii KJ, Muta T.
Title Screening of posttranscriptional regulatory molecules of IκB-ζ.
Journal Biochem Biophys Res Commun
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.
Volume 469(3)
Pages 711-5
Published 2016-1-15
DOI 10.1016/j.bbrc.2015.12.068
PII S0006-291X(15)31073-1
PMID 26711529
MeSH Adaptor Proteins, Signal Transducing Animals Base Sequence HEK293 Cells Humans I-kappa B Proteins / genetics* Interleukin-1beta / genetics* Mice Molecular Sequence Data Myeloid Differentiation Factor 88 / genetics* Nuclear Proteins / genetics* Peptide Fragments / genetics* RAW 264.7 Cells RNA Processing, Post-Transcriptional / genetics* RNA Stability / genetics* Regulatory Elements, Transcriptional / genetics*
IF 2.985
Times Cited 2
DNA material pcDNA3-Myc-mouse MyD88N (RDB16740) pGL4.12 SV40-mouse IkBzeta 3`UTR (full) (RDB16738) pGL4.12 SV40-mouse IkBzeta 3`UTR (165nt) (RDB16739)