CD28-Mediated regulation of mRNA stability requires sequences within the coding region of the IL-2 mRNA.
Using sequence-tagged genomic reporter constructs, we investigated the contribution of IL-2 sequences to CD28-mediated regulation of mRNA stability. We find that CD28 signaling acts transiently to stabilize the IL-2 mRNA following T cell activation. Such stabilization requires sequences within both exon 2 and the coding region of exon 4. Unexpectedly, CD28 signaling at later times enhances the decay of the IL-2 mRNA. This CD28-dependent decay of IL-2 mRNA requires sequences localized between exon 3 and the stop codon. Our findings demonstrate that the coding region of the IL-2 mRNA contains previously undefined CD28-responsive sequence elements that are critical for the regulation of mRNA stability.
Ragheb
J A
JA
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Deen
M
M
Schwartz
R H
RH
D020413:3' Untranslated Regions / Q000235:genetics / Q000276:immunology; D000818:Animals; D018106:CD28 Antigens / Q000502:physiology*; D002999:Clone Cells; D005091:Exons / Q000235:genetics / Q000276:immunology*; D017930:Genes, Reporter / Q000276:immunology; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000276:immunology; D007376:Interleukin-2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016324:Sequence Tagged Sites; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014162:Transfection / Q000276:immunology
D020413:3' Untranslated Regions; D018106:CD28 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger