Transcriptional regulation of meiosis in budding yeast

1993). Nevertheless, when Ime1 is tethered to heterologous genes it functions as a potent
transcriptional activator (Mandel et al., 1994; Smith et al., 1993).
As described above, the transcription of IME1 is subject to extensive regulation by the MAT
alleles and nutrients. On top of it, translation of IME1 mRNA is regulated by nutrients (Sherman
et al., 1993). In vegetative growth media with acetate as the sole carbon source low but
substantial levels of IME1 or ime1-lacZ mRNAs are observed, but Ime1-lacZ protein is not
detected. On the other hand, upon nitrogen depletion, the level of IME1 mRNA is not induced in
MATa/MATa cells, but Ime1-lacZ protein is readily observed (Sherman et al., 1993). Furthermore,
α-factor and heat-shock treatment increases the transcription of IME1, but translation occurs only
in cells arrested in G1 by either α-factor, or the CDC mutations cdc28-4 and cdc4-3 (Sherman et
al., 1993). These results suggest that nitrogen and/or cell cycle progression inhibits translation of
IME1 mRNA. Since nitrogen depletion leads to a G1 arrest, it is possible that the effect of
nitrogen is indirect, and that a G1 arrest is a prerequisite for efficient translation. IME1 has an
atypical 5 UTR (untranslated region), 229 bp long (Sherman et al., 1993), which might mediate
this regulation. Sequence analysis reveals that this RNA region can form stem-and-loop
secondary structure that might inhibit translation. However, deletion of this region has no effect
on the translation of IME1 mRNA (Ben- Dov, 1994). Thus, it is not known how nitrogen and/or
G1 phase controls the efficiency of translation of IME1 mRNA.
Over expression of Ime1 in acetate growth media does not induce meiosis and sporulation in
logarithmic cultures of wild-type diploids (Colomina et al., 1999; Sherman et al., 1993). On the
other hand, in diploid cells arrested in G1 by recessive temperature sensitive mutations in
CDC28, CDC4, CDC25, CDC35 (CYR1), or concomitant deletion of the three CLN genes, high
percentages of asci are formed (Colomina et al., 1999; Sherman et al., 1993; Shilo et al., 1978),
suggesting that post-translational modification of Ime1 or another factor required for meiosis
depends on lack of function of these proteins. Indeed, in vegetative cultures, depending on the
Cdc28/Cln function, Ime1 is phosphorylated and sequestered from the nucleus (Colomina et al.,
1999). The localization of Ime1 in the cytoplasm prevents its transcriptional activation function,
and entry into meiosis. Cdc4 is an F-box protein [for review see (Patton et al., 1998)] required for
degradation of specific targets in G1. Interestingly, one of its substrates is Far1, an inhibitor of
Cln/Cdc28 function (Henchoz et al., 1997). Thus, the effect of Cdc4 on sporulation may be
mediated through Cdc28/Cln function. The role of Cdc25 and Cdc35, the two positive regulators
of PKA on the function of Ime1 is most probably through their effect on the association of Ime1
with Ume6 (see below).
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