The cap structure and the poly(A) tail synergistically
activate mRNA translation in vivo. Recent work using Saccharomyces
cerevisiae spheroplasts and a yeast cell-free translation
system revealed that the poly(A) tail can function as an
independent promotor for ribosome recruitment, to internal
initiation sites within an mRNA. This raises the question
of how regulatory upstream open reading frames and translational
repressor proteins binding to the 5′ UTR can function,
as well as how regulated polyadenylation can support faithful
activation of protein synthesis. We investigated the function
of the regulatory upstream open reading frame 4 from the
yeast GCN 4 gene and the effect of IRP-1 binding to an
iron-responsive element introduced into the 5′ UTR
of reporter mRNAs. Both manipulations effectively block
cap-dependent translation, whereas ribosome recruitment
promoted by the poly(A) tail under noncompetitive conditions
can efficiently bypass both blocks. We show that the synergistic
use of both, the cap structure and the poly-A tail enforced
by mRNA competition reinstates the full extent of translational
control by both types of 5′ UTR regulatory elements.
With a view towards regulated polyadenylation, we studied
the function of poly(A) tails of defined length on the
translation of capped mRNAs. We find that poly(A) tail
elongation increases translational efficiency, particularly
under competitive conditions. Our results integrate recent
findings on the function of the poly(A) tail into an understanding
of translational control.