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Nuclear envelope protein MAN1 regulates clock through BMAL1.

Lin ST, Zhang L, Lin X, Zhang LC, Garcia VE, Tsai CW, Ptáček L, Fu YH - Elife (2014)

Bottom Line: Our knowledge of these components and pathways is far from exhaustive.In recent decades, the nuclear envelope has emerged as a global gene regulatory machine, although its role in circadian regulation has not been explored.Our results establish a novel connection between the nuclear periphery and circadian rhythmicity, therefore bridging two global regulatory systems that modulate all aspects of bodily functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.

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Related in: MedlinePlus

The mRNA levels of nuclear envelope genes are reduced in the corresponding knockdown flies.Plots of relative mRNA abundance for MAN1, Lam, and LBR from whole head extracts of timGAL4/+;UASdicer2/+, timGAL4/UASMAN1RNAi;UASdicer2/+, timGAL4/+;UASdicer2/UASLamRNAi and timGAL4/UASLBRRNAi;UASdicer2/+ flies determined by qRT-PCR. Error bars represent SEM (n = 3–6). Significant differences indicated by asterisks (Student's t test, *p < 0.05, **p < 0.01, ***p < 0.001). The value of timGAL4/+;UASdicer2/+ for one experiment was set to 1.DOI:http://dx.doi.org/10.7554/eLife.02981.007
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fig2s2: The mRNA levels of nuclear envelope genes are reduced in the corresponding knockdown flies.Plots of relative mRNA abundance for MAN1, Lam, and LBR from whole head extracts of timGAL4/+;UASdicer2/+, timGAL4/UASMAN1RNAi;UASdicer2/+, timGAL4/+;UASdicer2/UASLamRNAi and timGAL4/UASLBRRNAi;UASdicer2/+ flies determined by qRT-PCR. Error bars represent SEM (n = 3–6). Significant differences indicated by asterisks (Student's t test, *p < 0.05, **p < 0.01, ***p < 0.001). The value of timGAL4/+;UASdicer2/+ for one experiment was set to 1.DOI:http://dx.doi.org/10.7554/eLife.02981.007

Mentions: The effects of NE proteins on Drosophila circadian clock were also examined. Consistent with the mammalian data, over-expressing dLamin (dLam) (Padiath et al., 2006) in circadian neurons with cryptochrome (cry)GAL4-39 and cryGAL4-16 (Emery et al., 2000) in vivo resulted in substantially shortened periods of behavioral rhythms in constant darkness compared to GAL4 controls (but not to UASLMNB1/+, Table 1; Figure 2—figure supplement 1A). Knocking down dLam in circadian neurons lengthened the period (Table 2; Figure 2—figure supplement 1B). On the other hand, over-expressing dMAN1 and dLBR lengthened the period (Table 1; Figure 2—figure supplement 1A), while knocking down dMAN1 also lengthened period (Table 2; Figure 2—figure supplement 1B). Besides altering the period, most of these manipulations reduced the amplitude of behavioral rhythms as indicated by the reduced power values. In addition, we have assessed the mRNA levels of dMAN1, dLam, and dLBR to confirm knockdown (Figure 2—figure supplement 2). Taken together, these results indicate that NE proteins also participate in the regulation of fly clock.10.7554/eLife.02981.008Table 1.


Nuclear envelope protein MAN1 regulates clock through BMAL1.

Lin ST, Zhang L, Lin X, Zhang LC, Garcia VE, Tsai CW, Ptáček L, Fu YH - Elife (2014)

The mRNA levels of nuclear envelope genes are reduced in the corresponding knockdown flies.Plots of relative mRNA abundance for MAN1, Lam, and LBR from whole head extracts of timGAL4/+;UASdicer2/+, timGAL4/UASMAN1RNAi;UASdicer2/+, timGAL4/+;UASdicer2/UASLamRNAi and timGAL4/UASLBRRNAi;UASdicer2/+ flies determined by qRT-PCR. Error bars represent SEM (n = 3–6). Significant differences indicated by asterisks (Student's t test, *p < 0.05, **p < 0.01, ***p < 0.001). The value of timGAL4/+;UASdicer2/+ for one experiment was set to 1.DOI:http://dx.doi.org/10.7554/eLife.02981.007
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fig2s2: The mRNA levels of nuclear envelope genes are reduced in the corresponding knockdown flies.Plots of relative mRNA abundance for MAN1, Lam, and LBR from whole head extracts of timGAL4/+;UASdicer2/+, timGAL4/UASMAN1RNAi;UASdicer2/+, timGAL4/+;UASdicer2/UASLamRNAi and timGAL4/UASLBRRNAi;UASdicer2/+ flies determined by qRT-PCR. Error bars represent SEM (n = 3–6). Significant differences indicated by asterisks (Student's t test, *p < 0.05, **p < 0.01, ***p < 0.001). The value of timGAL4/+;UASdicer2/+ for one experiment was set to 1.DOI:http://dx.doi.org/10.7554/eLife.02981.007
Mentions: The effects of NE proteins on Drosophila circadian clock were also examined. Consistent with the mammalian data, over-expressing dLamin (dLam) (Padiath et al., 2006) in circadian neurons with cryptochrome (cry)GAL4-39 and cryGAL4-16 (Emery et al., 2000) in vivo resulted in substantially shortened periods of behavioral rhythms in constant darkness compared to GAL4 controls (but not to UASLMNB1/+, Table 1; Figure 2—figure supplement 1A). Knocking down dLam in circadian neurons lengthened the period (Table 2; Figure 2—figure supplement 1B). On the other hand, over-expressing dMAN1 and dLBR lengthened the period (Table 1; Figure 2—figure supplement 1A), while knocking down dMAN1 also lengthened period (Table 2; Figure 2—figure supplement 1B). Besides altering the period, most of these manipulations reduced the amplitude of behavioral rhythms as indicated by the reduced power values. In addition, we have assessed the mRNA levels of dMAN1, dLam, and dLBR to confirm knockdown (Figure 2—figure supplement 2). Taken together, these results indicate that NE proteins also participate in the regulation of fly clock.10.7554/eLife.02981.008Table 1.

Bottom Line: Our knowledge of these components and pathways is far from exhaustive.In recent decades, the nuclear envelope has emerged as a global gene regulatory machine, although its role in circadian regulation has not been explored.Our results establish a novel connection between the nuclear periphery and circadian rhythmicity, therefore bridging two global regulatory systems that modulate all aspects of bodily functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of California, San Francisco, San Francisco, United States.

Show MeSH
Related in: MedlinePlus