Biosynthesis of human acute-phase serum amyloid A protein (A-SAA) in vitro: The roles of mRNA accumulation, poly(A) tail shortening and translational efficiency

D. M. Steel, J. T. Rogers, M. C. DeBeer, F. C. DeBeer, A. S. Whitehead

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Human 'acute-phase' serum amyloid A protein (A-SAA) is a major acute-phase reactant (APR) and an apolipoprotein of high density lipoprotein 3 (HDL3). We have examined several parameters of A-SAA biosynthesis in PLC/PRF/5 hepatoma cells in response to monocyte conditioned medium (MoCM) and dual treatment with interleukin-1β and interleukin-6 (IL-1β+IL-6). Treatment of PLC/PRF/5 cells with MoCM or IL-1β+IL-6 caused a dramatic and rapid increase in A-SAA mRNA and protein synthesis; A-SAA mRNA was first detectable at 3h, with peak levels reached by 24h. A-SAA mRNA accumulation is accompanied by a gradual and homogeneous decrease in the length of the A-SAA poly(A) tail; the poly(A) tail shortening does not apparently affect the intrinsic stability of A-SAA mRNA. Analysis of RNA isolated from the ribonucleoprotein, monosome and polysome fractions of cytokine-treated PLC/PRF/5 cells showed that most A-SAA mRNA was associated with small polyribosomes, regardless of time post-stimulus, suggesting that the translational efficiency of A-SAA mRNA is constant throughout cytokine-driven induction. Moreover, the transit time of A-SAA protein out of the cell is also constant throughout the time course of induction. These data provide evidence of a paradox with regard to the transcriptional upregulation of A-SAA by IL-1β+IL-6 and the relative synthesis of A-SAA protein and suggest a role for post-transcriptional control of A-SAA biosynthesis during the acute phase.

Original languageEnglish
Pages (from-to)701-707
Number of pages7
JournalBiochemical Journal
Volume291
Issue number3
DOIs
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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