BIOSYNTHESIS OF HUMAN ACUTE-PHASE SERUM AMYLOID A-PROTEIN (A-SAA) INVITRO - THE ROLES OF MESSENGER-RNA ACCUMULATION, POLY(A) TAIL SHORTENING AND TRANSLATIONAL EFFICIENCY
Dm. Steel et al., BIOSYNTHESIS OF HUMAN ACUTE-PHASE SERUM AMYLOID A-PROTEIN (A-SAA) INVITRO - THE ROLES OF MESSENGER-RNA ACCUMULATION, POLY(A) TAIL SHORTENING AND TRANSLATIONAL EFFICIENCY, Biochemical journal, 291, 1993, pp. 701-707
Human 'acute-phase' serum amyloid A protein (A-SAA) is a major acute-p
hase 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-1beta and interleukin-6 (IL-
1beta+IL-6). Treatment of PLC/PRF/5 cells with MoCM or IL-1beta+IL-6 c
aused a dramatic and rapid increase in A-SAA mRNA and protein synthesi
s; A-SAA mRNA was first detectable at 3 h, with peak levels reached by
24 h. A-SAA mRNA accumulation is accompanied by a gradual and homogen
eous decrease in the length of the A-SAA poly(A) tail; the poly(A) tai
l shortening does not apparently affect the intrinsic stability of A-S
AA mRNA. Analysis of RNA isolated from the ribonucleoprotein, monosome
and polysome fractions of cytokine-treated PLC/PRF/5 cells showed tha
t 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 t
hroughout the time course of induction. These data provide evidence of
a paradox with regard to the transcriptional up-regulation of A-SAA b
y IL-1beta+IL-6 and the relative synthesis of A-SAA protein and sugges
t a role for post-transcriptional control of A-SAA biosynthesis during
the acute phase.