An inducible cytoplasmic factor (AU-B) binds selectively to AUUUA multimers in the 3' untranslated region of lymphokine mRNA.
Considerable evidence suggests that the metabolism of lymphokine mRNAs can be selectively regulated within the cytoplasm. However, little is known about the mechanism(s) that cells use to discriminate lymphokine mRNAs from other mRNAs within the cytoplasm. In this study we report a sequence-specific cytoplasmic factor (AU-B) that binds specifically to AUUUA multimers present in the 3' untranslated region of lymphokine mRNAs. AU-B does not bind to monomeric AUUUA motifs nor to other AU-rich sequences present in the 3' untranslated region of c-myc mRNA. AU-B RNA-binding activity is not present in quiescent T cells but is rapidly induced by stimulation of the T-cell receptor/CD3 complex. Induction of AU-B RNA-binding activity requires new RNA and protein synthesis. Stabilization of lymphokine mRNA induced by costimulation with phorbol myristate acetate correlates inversely with binding by AU-B. Together, these data suggest that AU-B is a cytoplasmic regulator of lymphokine mRNA metabolism.
Bohjanen
P R
PR
Cellular and Molecular Biology Program, Howard Hughes Medical Institute, Ann Arbor, Michigan.
Petryniak
B
B
June
C H
CH
Thompson
C B
CB
Lindsten
T
T
D001483:Base Sequence; D001665:Binding Sites; D001685:Biological Factors / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D016259:Genes, myc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D008222:Lymphokines / Q000235:genetics*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D001685:Biological Factors; D007376:Interleukin-2; D008222:Lymphokines; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate