A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements.
The control of mRNA stability is crucial to the regulation of cytokine expression. We describe here a novel, potent destabilizing element found in the 3' untranslated region of granulocyte colony-stimulating factor mRNA. This element, which appears to require at least one stem-loop structure, we term the stem-loop destabilizing element (SLDE). Functionally equivalent elements appear to also exist in the interleukin 2 and interleukin 6 mRNAs. The SLDE is functionally distinct from the A+U-rich elements, which are also present in these and other cytokine mRNAs, because it destabilizes a chimeric mRNA in a tumor cell line in which A+U-rich elements do not function. In addition, the effect of the SLDE is insensitive to calcium ionophore and is therefore regulated independently of A+U destabilizing elements. The existence of two distinct mRNA-destabilizing elements provides an additional mechanism for the differential regulation of cytokine expression.
Brown
C Y
CY
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia.
Lagnado
C A
CA
Goodall
G J
GJ
D016475:3T3 Cells; D000225:Adenine; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D000001:Calcimycin / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis*; D018076:DNA, Complementary; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D019382:Human Growth Hormone / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014498:Uracil
D016207:Cytokines; D018076:DNA, Complementary; D007376:Interleukin-2; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D016179:Granulocyte Colony-Stimulating Factor; D000001:Calcimycin; D014498:Uracil; D000225:Adenine