The MLA 144 gibbon T cell line is infected with a type C retrovirus and constitutively expresses interleukin-2 (IL-2) and granulocyte macrophage colony-stimulating factor (GM-CSF). IL-2 mRNA levels are 10-fold more abundant than GM-CSF in these cells. Comparable transcriptional rates for these lymphokines suggested the involvement of post-transcriptional mechanisms in selective IL-2 mRNA accumulation. IL-2 mRNA is exceptionally stable in MLA cells with a t1/2 of more than 8 h. The presence of reiterated AUUUA sequences in the 3′-untranslated region (UTR) has been shown to confer mRNA lability. The provirally altered MLA IL-2 allele encodes an mRNA in which three AUUUA motifs have been deleted. Six major cytoplasmic proteins bound in vitro transcribed RNA probes containing sequences from the 3′-UTR of normal human IL-2 (3′-IL-2), GM-CSF (Δ2R1), and the virally altered MLA IL-2 (3′-IL-2 PV) mRNA. Increased binding of these proteins to 3′-IL-2 PV was observed relative to 3′-IL-2 or Δ2R1. Northwestern blotting demonstrated similar differential ability of a 36- and 43-kDa protein to bind, as well as showed that these proteins colocalized by immunoblotting as hnRNP A1 and C, respectively. These findings suggest a direct correlation between differential binding of cytoplasmic proteins to AU-rich 3′-UTRs in vitro and lymphokine mRNA stability in vivo.
CITATION STYLE
Henics, T., Sanfridson, A., Hamilton, B. J. N., Nagy, E., & Rigby, W. F. C. (1994). Enhanced stability of interleukin-2 mRNA in MLA 144 cells: Possible role of cytoplasmic AU-rich sequence-binding proteins. Journal of Biological Chemistry, 269(7), 5377–5383. https://doi.org/10.1016/s0021-9258(17)37697-4
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