Biology Reference
In-Depth Information
rates increase, most likely because the stress induced by glucose-galactose shift
increases transcript degradation rates (see Step 2 in Fig.
12.4
) more than what can be
compensated for by increased transcription. During Phases II and III, the glycolytic
transcript levels decrease by twofold, whereas the oxidative phosphorylation
(oxphos) transcript levels increase by fourfold. Since the corresponding transcription
rates of both the glycolytic and respiratory genes decline rapidly followed by a
plateau, the increased respiratory (also called oxphos) mRNA levels cannot be
accounted for in terms of transcriptional control alone but must implicate
degradational control as well. That is, just as the removal of glucose “de-induces”
glycolytic mRNA molecules (leading to the declining TL and TR trajectories
for glycolysis seen in Fig.
12.2a
, b), so it might repress (or de-induce) the degradation
of respiratory mRNAmolecules, leading to a rise in respiratory mRNA levels as seen
in Fig.
12.2a
between 5 and 360 min. This hypothetical phenomenon may be referred
to as
glucose de-induction
in analogy to
glucose induction
(Winderickx et al. 2002;
Ronne 1995). During Phase IV, both TL and TR for glycolytic and respiratory genes
increase, and this may be attributed to galactose induction of the Leloir transcription
(Fu et al. 1995; Leuther and Johnston 1992). In support of this interpretation, it was
found that glucose-galactose shift induced an increase in both TL and TR of the
Leloir genes (GAL 1, 2, 3, 7, and 10) between 120 and 450 min by more than tenfold
(see Fig.
12.3
). The Leloir genes code for the enzymes and transport proteins that
are involved in converting extracellular galactose to intracellular glucose-1-
phosphate (Berg et al. 2002), which is then metabolized via the glycolytic and
respiratory pathways. Finally, during Phase V, the glycolytic mRNA levels remain
constant while the respiratory mRNA levels decline slightly, the latter likely due to
galactose repression (in analogy to the glucose repression [Winderickx et al. 2002])
of respiration following the formation of glucose-1-phosphate via the Leloir pathway
(Berg et al. 2002). The transcription rate of glycolytic genes continue to increase
during Phase V probably due to galactose induction (Fu et al. 1995; Leuther and
Johnston 1992), although the corresponding transcript levels remain unchanged,
which may indicate the degradational control of glycolytic mRNA molecules. That
is, budding yeast seems capable of keeping glycolytic TL constant in the face
of increasing TR, by increasing the transcript degradation rates (TD). The TR
trajectory of respiratory genes also continue to increase during Phase V despite the
fact that their TL trajectory decline, which can be best explained in terms of
the hypothesis that respiratory mRNA levels are controlled by transcript degradation
during this time period. It is evident that the TL and TR data presented in Fig.
12.2a
,b
cannot be adequately accounted for in terms of TR alone but requires taking into
account both TR and TD (transcript degradation) on an equal footing (Ji et al. 2009a).
12.5 The IDS-Cell Function Identity Hypothesis:
Experimental Evidence
Since RNA levels reflect the dynamic metabolic states of cells (or
cell states
)resulting
from the interaction between two opposing processes -
transcription
and
transcript
degradation
(see Fig.
12.4
) - their maintenance requires free energy dissipation.
