In the experiments described above, two of the characteristics of the autoregulatory circuit of mammalian antizyme 1 were con®rmed: SPA inhibition of ODC and the +1 translational frameshifting. The key question left is whether the recoding event is responsive to polyamine levels in cells. As shown above, overexpression of SPA leads to signi®cant reduction of polyamine levels in S.pombe. An SPA + strain was co-transformed with an SPA wild-type overexpressing plasmid (cells overexpressing wild-type SPA grow slowly but continuously) and a construct that monitors the +1 frameshifting from an SPA frameshift sequence. The +1 frameshifting was compared with that in SPA non-overexpressing cells (in both cases frameshifting was measured relative to in-frame control). The results ( Figure 6 ) show a signi®cant reduction (6.5-fold) in frameshifting ef®ciency in SPA-overproducing cells that correlates with a decrease of polyamine content (4.5-fold for putrescine and 3.9-fold for spermidine). This indicates that polyamines modulate the frameshifting ef®ciency of SPA. An alternative but less likely possibility is that SPA overexpression reduces frameshifting because high levels of SPA transcript titrate some factor limiting for frameshifting.