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Isoform switching facilitates period control in the Neurospora crassa circadian clock.

Akman OE, Locke JC, Tang S, Carré I, Millar AJ, Rand DA - Mol. Syst. Biol. (2008)

Bottom Line: Moreover, given that many biological rate constants have a Q(10) of around 2, it is remarkable that such clocks remain rhythmic under significant temperature changes.We introduce a new mathematical model for the Neurospora crassa circadian network incorporating experimental work showing that temperature alters the balance of translation between a short and long form of the FREQUENCY (FRQ) protein.We present a simple mechanism utilising the presence of the FRQ isoforms (isoform switching) by which period control could have evolved, and argue that this regulatory structure may also increase the temperature range where the clock is robustly rhythmic.

View Article: PubMed Central - PubMed

Affiliation: Centre for Systems Biology at Edinburgh, The University of Edinburgh, Edinburgh, UK [corrected]

ABSTRACT
A striking and defining feature of circadian clocks is the small variation in period over a physiological range of temperatures. This is referred to as temperature compensation, although recent work has suggested that the variation observed is a specific, adaptive control of period. Moreover, given that many biological rate constants have a Q(10) of around 2, it is remarkable that such clocks remain rhythmic under significant temperature changes. We introduce a new mathematical model for the Neurospora crassa circadian network incorporating experimental work showing that temperature alters the balance of translation between a short and long form of the FREQUENCY (FRQ) protein. This is used to discuss period control and functionality for the Neurospora system. The model reproduces a broad range of key experimental data on temperature dependence and rhythmicity, both in wild-type and mutant strains. We present a simple mechanism utilising the presence of the FRQ isoforms (isoform switching) by which period control could have evolved, and argue that this regulatory structure may also increase the temperature range where the clock is robustly rhythmic.

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Dependence of period on temperature for the Neurospora model. Circles denote the WT. Left panel: mutant strains obtained through optimisation or suppression of splicing (Diernfellner et al, 2005, 2007). Inverted triangles: strain A; triangles: strain A with divergent FRQ pathways; diamonds: strain B; squares: strain B with divergent FRQ pathways. For the simulations obtained assuming FRQ pathway asymmetry, strain A has an increasing period–temperature profile, while strain B has a decreasing one with the period of strain A greater than that of strain B, as observed experimentally (Diernfellner et al, 2007). Right panel: mutant strains obtained through modification of the l-FRQ AUG or s-FRQ coding region (Liu et al, 1997). Triangles: strain C; squares: strain D. Strain is compensated at lower temperatures with a period greater than that of the wild-type, becoming arrhythmic at the upper end of the range. Strain D is compensated at higher temperatures with a period smaller than that of the WT, becoming arrhythmic at the lower end of the range. This is in agreement with experimental data (Liu et al, 1997).
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f3: Dependence of period on temperature for the Neurospora model. Circles denote the WT. Left panel: mutant strains obtained through optimisation or suppression of splicing (Diernfellner et al, 2005, 2007). Inverted triangles: strain A; triangles: strain A with divergent FRQ pathways; diamonds: strain B; squares: strain B with divergent FRQ pathways. For the simulations obtained assuming FRQ pathway asymmetry, strain A has an increasing period–temperature profile, while strain B has a decreasing one with the period of strain A greater than that of strain B, as observed experimentally (Diernfellner et al, 2007). Right panel: mutant strains obtained through modification of the l-FRQ AUG or s-FRQ coding region (Liu et al, 1997). Triangles: strain C; squares: strain D. Strain is compensated at lower temperatures with a period greater than that of the wild-type, becoming arrhythmic at the upper end of the range. Strain D is compensated at higher temperatures with a period smaller than that of the WT, becoming arrhythmic at the lower end of the range. This is in agreement with experimental data (Liu et al, 1997).

Mentions: Simulated variations of period with temperature for the WT and strains A-D are shown in Figure 3. For the basic near-symmetric model, all parameters of the l-FRQ and s-FRQ pathways except for those controlling translation rates are approximately equal. This reproduced the main features of the WT and strains C and D including the dependence of period upon temperature. However, to reproduce the temperature-dependent increase in period that has been observed experimentally for strain A (Diernfellner et al, 2005, 2007), it was necessary to allow some parameters of the l-FRQ pathway to vary significantly from those of the s-FRQ pathway (see Supplementary information, section 5).


Isoform switching facilitates period control in the Neurospora crassa circadian clock.

Akman OE, Locke JC, Tang S, Carré I, Millar AJ, Rand DA - Mol. Syst. Biol. (2008)

Dependence of period on temperature for the Neurospora model. Circles denote the WT. Left panel: mutant strains obtained through optimisation or suppression of splicing (Diernfellner et al, 2005, 2007). Inverted triangles: strain A; triangles: strain A with divergent FRQ pathways; diamonds: strain B; squares: strain B with divergent FRQ pathways. For the simulations obtained assuming FRQ pathway asymmetry, strain A has an increasing period–temperature profile, while strain B has a decreasing one with the period of strain A greater than that of strain B, as observed experimentally (Diernfellner et al, 2007). Right panel: mutant strains obtained through modification of the l-FRQ AUG or s-FRQ coding region (Liu et al, 1997). Triangles: strain C; squares: strain D. Strain is compensated at lower temperatures with a period greater than that of the wild-type, becoming arrhythmic at the upper end of the range. Strain D is compensated at higher temperatures with a period smaller than that of the WT, becoming arrhythmic at the lower end of the range. This is in agreement with experimental data (Liu et al, 1997).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2267733&req=5

f3: Dependence of period on temperature for the Neurospora model. Circles denote the WT. Left panel: mutant strains obtained through optimisation or suppression of splicing (Diernfellner et al, 2005, 2007). Inverted triangles: strain A; triangles: strain A with divergent FRQ pathways; diamonds: strain B; squares: strain B with divergent FRQ pathways. For the simulations obtained assuming FRQ pathway asymmetry, strain A has an increasing period–temperature profile, while strain B has a decreasing one with the period of strain A greater than that of strain B, as observed experimentally (Diernfellner et al, 2007). Right panel: mutant strains obtained through modification of the l-FRQ AUG or s-FRQ coding region (Liu et al, 1997). Triangles: strain C; squares: strain D. Strain is compensated at lower temperatures with a period greater than that of the wild-type, becoming arrhythmic at the upper end of the range. Strain D is compensated at higher temperatures with a period smaller than that of the WT, becoming arrhythmic at the lower end of the range. This is in agreement with experimental data (Liu et al, 1997).
Mentions: Simulated variations of period with temperature for the WT and strains A-D are shown in Figure 3. For the basic near-symmetric model, all parameters of the l-FRQ and s-FRQ pathways except for those controlling translation rates are approximately equal. This reproduced the main features of the WT and strains C and D including the dependence of period upon temperature. However, to reproduce the temperature-dependent increase in period that has been observed experimentally for strain A (Diernfellner et al, 2005, 2007), it was necessary to allow some parameters of the l-FRQ pathway to vary significantly from those of the s-FRQ pathway (see Supplementary information, section 5).

Bottom Line: Moreover, given that many biological rate constants have a Q(10) of around 2, it is remarkable that such clocks remain rhythmic under significant temperature changes.We introduce a new mathematical model for the Neurospora crassa circadian network incorporating experimental work showing that temperature alters the balance of translation between a short and long form of the FREQUENCY (FRQ) protein.We present a simple mechanism utilising the presence of the FRQ isoforms (isoform switching) by which period control could have evolved, and argue that this regulatory structure may also increase the temperature range where the clock is robustly rhythmic.

View Article: PubMed Central - PubMed

Affiliation: Centre for Systems Biology at Edinburgh, The University of Edinburgh, Edinburgh, UK [corrected]

ABSTRACT
A striking and defining feature of circadian clocks is the small variation in period over a physiological range of temperatures. This is referred to as temperature compensation, although recent work has suggested that the variation observed is a specific, adaptive control of period. Moreover, given that many biological rate constants have a Q(10) of around 2, it is remarkable that such clocks remain rhythmic under significant temperature changes. We introduce a new mathematical model for the Neurospora crassa circadian network incorporating experimental work showing that temperature alters the balance of translation between a short and long form of the FREQUENCY (FRQ) protein. This is used to discuss period control and functionality for the Neurospora system. The model reproduces a broad range of key experimental data on temperature dependence and rhythmicity, both in wild-type and mutant strains. We present a simple mechanism utilising the presence of the FRQ isoforms (isoform switching) by which period control could have evolved, and argue that this regulatory structure may also increase the temperature range where the clock is robustly rhythmic.

Show MeSH
Related in: MedlinePlus