Mechanism-based Clustering of Genome-wide RNA Levels: Roles of Transcription and Transcript-Degradation Rates - Clustering Challenges in Biological Network - page 250

an increase in both TL and TR of the Leloir genes (GAL 1, 2, 3, 7 and 10) be-
tween 120 and 450 minutes by more than 10 folds (data not shown). The Leloir
genes code for the enzymes and transport proteins that are involved in convert-
ing extracellular galactose to intracellular glucose-1-phosphate [9], which is then
metabolized via the glycolytic and respiratory pathways. Finally, during Phase
V, the glycolytic mRNA levels remain constant while the respiratory mRNA lev-
els decline slightly, the latter probably due to galactose repression (in analogy
to the well-known glucose repression [18]) of respiration following the forma-
tion of glucose-1-phosphate via the Leloir pathway [9]. The transcription rate of
glycolytic genes continue to increase during Phase V probably due to galactose in-
duction [21, 25], although the corresponding transcript levels remain unchanged,
which may also indicate the degradational control of glycolytic mRNA molecules
during this time period. That is, budding yeast seems able to keep glycolytic TL
constant in the face of increasing TR , by increasing TD - the transcript degradation
rate. 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 that respiratory mRNA levels are controlled by
transcript degradation. It is quite evident that the TL and TR data presented in
Fig. 12.3a and 12.3b cannot be accounted for in terms of TR alone but requires
taking into account both TR and TD on an equal footing for their logically consis-
tent explications, which is tantamount to the conclusion that TL is determined by
the D/T ratio (see Fig. 12.3a and 12.4).

Table 12.2. A summary of the kinetics of the TL and TR changes depicted in Fig. 12.3a
and 12.3b. The upward and downward arrows indicate an increase and decrease, respectively.
Time (min) 0-5 5-120 120-360 360-450 450-850

Phase (or Time Period) I II III IV V

Transcript Glycolysis ↓ ↓ ↓ ↑ No Change

Level (TL) Oxidative ↓ ↑ ↑ ↑ ↓

Phosphorylation

Transcription Glycolysis ↑ ↓ ↓ ↑ ↑

↑ ↓ ↓ ↑ ↑

Rate (TR) Oxidative

Phosphorylation

In conclusion, the genome-wide TL and TR data of S. cerevisiae measured by
Garcia-Martinez et al. [10] have provided us with a concrete experimental basis
to establish the concept that mRNA levels measured with cDNA arrays cannot be
interpreted in terms other than what is here called the transcription/degradation
( D/T ) ratios. These ratios have been found useful in characterizing the temporal
evolution of the molecular mechanisms underlying mRNA level changes induced