Md. Sheets et al., THE 3'-UNTRANSLATED REGIONS OF C-MOS AND CYCLIN MESSENGER-RNAS STIMULATE TRANSLATION BY REGULATING CYTOPLASMIC POLYADENYLATION, Genes & development, 8(8), 1994, pp. 926-938
Early in the development of many animals, before transcription begins,
any change in the pattern of protein synthesis is attributable to a c
hange in the translational activity or stability of an mRNA in the egg
. As a result, translational control is critical for a variety of deve
lopmental decisions, including axis formation in Drosophila and sex de
termination in Caenorhabditis elegans. Previous work demonstrated that
increases in poly(A) length can activate translation, whereas removal
of poly(A) can prevent it. In this report we focus on the control of
c-mos and cyclin A1, B1, and B2 mRNAs during meiotic maturation and af
ter fertilization of frog eggs. We show that addition and removal of p
oly(A) from these mRNAs is extensively regulated: The time at which ea
ch mRNA receives or loses poly(A), as well as the number of adenosines
it gains or loses, differ substantially. Signals in the 3'-untranslat
ed region (UTR) of each mRNA are sufficient to reconstitute both the t
emporal and quantitative control of poly(A) addition: Chimeric mRNAs i
n which a luciferase-coding region is joined to the 3' UTRs of cyclin
A1, cyclin B1, or c-mos mRNA, receive poly(A) of the same length and a
t the same time as do the endogenous mRNAs. Moreover, each 3' UTR also
regulates translation of the chimeric mRNAs, determining when and how
much translation of the luciferase reporter is stimulated during matu
ration. The magnitude of stimulation in luciferase activity varies fro
m 5- to 100-fold, depending on the 3' UTR. Translational stimulation b
y each 3' UTR requires poly(A) lengthening, as it is prevented by muta
tions that prevent that process. These results suggest that the 3' UTR
s of cyclin and c-mos mRNAs control not only whether or not an mRNA is
turned on during maturation, but when that activation occurs and to w
hat extent. Translational control of c-mos mRNA, which may be achieved
through regulation of poly(A) length, may be critical in the activati
on of maturation, and in the onset of cleavage divisions. Our findings
, as well as those of others, suggest that even quite complex patterns
of translational activation in the early embryo can be attained throu
gh the differential control of a common mechanism.