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Global coordination of transcriptional control and mRNA decay during cellular differentiation.

Amorim MJ, Cotobal C, Duncan C, Mata J - Mol. Syst. Biol. (2010)

Bottom Line: Their levels and half-lives were reduced in meu5 mutants, demonstrating that Meu5p stabilizes its targets.In the absence of meu5, all Mei4p targets were expressed with similar kinetics, indicating that Meu5p alters the global features of the gene expression program.Our data provide insight into the topology of regulatory networks integrating transcriptional and posttranscriptional controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.

ABSTRACT
The function of transcription in dynamic gene expression programs has been extensively studied, but little is known about how it is integrated with RNA turnover at the genome-wide level. We investigated these questions using the meiotic gene expression program of Schizosaccharomyces pombe. We identified over 80 transcripts that co-purify with the meiotic-specific Meu5p RNA-binding protein. Their levels and half-lives were reduced in meu5 mutants, demonstrating that Meu5p stabilizes its targets. Most Meu5p-bound RNAs were also targets of the Mei4p transcription factor, which induces the transient expression of approximately 500 meiotic genes. Although many Mei4p targets showed sharp expression peaks, Meu5p targets had broad expression profiles. In the absence of meu5, all Mei4p targets were expressed with similar kinetics, indicating that Meu5p alters the global features of the gene expression program. As Mei4p activates meu5 transcription, Mei4p, Meu5p and their common targets form a feed-forward loop, a motif common in transcriptional networks but not studied in the context of mRNA decay. Our data provide insight into the topology of regulatory networks integrating transcriptional and posttranscriptional controls.

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Related in: MedlinePlus

Meu5p regulates the dynamics of expression of its targets. (A) Average expression profiles of ‘early-decrease' (left) or ‘late-decrease' (right) genes in pat1-induced meiotic time courses. Labelling of the graphs is as in Figure 4A, except that expression ratios were normalized to the levels at 3 h after the induction of meiosis in the corresponding experiment. Data from wild-type meiosis are shown in purple and from meu5Δ are shown in green. (B) Diagram summarizing the regulation of the expression of middle genes. Proteins are shown as ovals and transcripts are shown as curvy lines. All middle genes are induced transcriptionally by Mei4p. Meu5p stabilizes its targets allowing them to be expressed for longer, whereas middle genes not bound by Meu5p are induced more transiently. Mei4p induces the expression of meu5, and thus Mei4p, Meu5p and their common targets form a feed-forward network motif.
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f5: Meu5p regulates the dynamics of expression of its targets. (A) Average expression profiles of ‘early-decrease' (left) or ‘late-decrease' (right) genes in pat1-induced meiotic time courses. Labelling of the graphs is as in Figure 4A, except that expression ratios were normalized to the levels at 3 h after the induction of meiosis in the corresponding experiment. Data from wild-type meiosis are shown in purple and from meu5Δ are shown in green. (B) Diagram summarizing the regulation of the expression of middle genes. Proteins are shown as ovals and transcripts are shown as curvy lines. All middle genes are induced transcriptionally by Mei4p. Meu5p stabilizes its targets allowing them to be expressed for longer, whereas middle genes not bound by Meu5p are induced more transiently. Mei4p induces the expression of meu5, and thus Mei4p, Meu5p and their common targets form a feed-forward network motif.

Mentions: The results presented above suggest a model in which Meu5p stabilizes the RNAs of its targets, thus allowing them to persist for a longer period of time. A prediction of this hypothesis is that in the absence of meu5, ‘late-decrease' genes should behave as ‘early-decrease' genes. To test this hypothesis, we carried out meiotic time courses in pat1-synchronized wild-type and meu5Δ diploids (Figure 5A, average profiles are shown). As expected, the expression profiles of ‘early-decrease' genes were almost identical in wild-type and meu5Δ cells. ‘Late-decrease' genes displayed a wide expression profile in wild-type cells, similar to published results (Mata et al, 2002). By contrast, they reached a lower peak in the absence of meu5, and their levels decreased sharply after 5 h. Indeed, their profiles in meu5Δ cells became indistinguishable from those of ‘early-decrease' genes. Meu5p-mediated stabilization of its RNA targets would be expected to influence their protein levels. To verify this prediction, we monitored protein levels of several Mei4p targets over meiotic time courses by western blot, in both wild-type and meu5 mutant cells (Supplementary Figure S11). As predicted, the levels of proteins encoded by Meu5p targets were clearly reduced in meu5Δ cells, whereas those of other Mei4p targets were not affected.


Global coordination of transcriptional control and mRNA decay during cellular differentiation.

Amorim MJ, Cotobal C, Duncan C, Mata J - Mol. Syst. Biol. (2010)

Meu5p regulates the dynamics of expression of its targets. (A) Average expression profiles of ‘early-decrease' (left) or ‘late-decrease' (right) genes in pat1-induced meiotic time courses. Labelling of the graphs is as in Figure 4A, except that expression ratios were normalized to the levels at 3 h after the induction of meiosis in the corresponding experiment. Data from wild-type meiosis are shown in purple and from meu5Δ are shown in green. (B) Diagram summarizing the regulation of the expression of middle genes. Proteins are shown as ovals and transcripts are shown as curvy lines. All middle genes are induced transcriptionally by Mei4p. Meu5p stabilizes its targets allowing them to be expressed for longer, whereas middle genes not bound by Meu5p are induced more transiently. Mei4p induces the expression of meu5, and thus Mei4p, Meu5p and their common targets form a feed-forward network motif.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2913401&req=5

f5: Meu5p regulates the dynamics of expression of its targets. (A) Average expression profiles of ‘early-decrease' (left) or ‘late-decrease' (right) genes in pat1-induced meiotic time courses. Labelling of the graphs is as in Figure 4A, except that expression ratios were normalized to the levels at 3 h after the induction of meiosis in the corresponding experiment. Data from wild-type meiosis are shown in purple and from meu5Δ are shown in green. (B) Diagram summarizing the regulation of the expression of middle genes. Proteins are shown as ovals and transcripts are shown as curvy lines. All middle genes are induced transcriptionally by Mei4p. Meu5p stabilizes its targets allowing them to be expressed for longer, whereas middle genes not bound by Meu5p are induced more transiently. Mei4p induces the expression of meu5, and thus Mei4p, Meu5p and their common targets form a feed-forward network motif.
Mentions: The results presented above suggest a model in which Meu5p stabilizes the RNAs of its targets, thus allowing them to persist for a longer period of time. A prediction of this hypothesis is that in the absence of meu5, ‘late-decrease' genes should behave as ‘early-decrease' genes. To test this hypothesis, we carried out meiotic time courses in pat1-synchronized wild-type and meu5Δ diploids (Figure 5A, average profiles are shown). As expected, the expression profiles of ‘early-decrease' genes were almost identical in wild-type and meu5Δ cells. ‘Late-decrease' genes displayed a wide expression profile in wild-type cells, similar to published results (Mata et al, 2002). By contrast, they reached a lower peak in the absence of meu5, and their levels decreased sharply after 5 h. Indeed, their profiles in meu5Δ cells became indistinguishable from those of ‘early-decrease' genes. Meu5p-mediated stabilization of its RNA targets would be expected to influence their protein levels. To verify this prediction, we monitored protein levels of several Mei4p targets over meiotic time courses by western blot, in both wild-type and meu5 mutant cells (Supplementary Figure S11). As predicted, the levels of proteins encoded by Meu5p targets were clearly reduced in meu5Δ cells, whereas those of other Mei4p targets were not affected.

Bottom Line: Their levels and half-lives were reduced in meu5 mutants, demonstrating that Meu5p stabilizes its targets.In the absence of meu5, all Mei4p targets were expressed with similar kinetics, indicating that Meu5p alters the global features of the gene expression program.Our data provide insight into the topology of regulatory networks integrating transcriptional and posttranscriptional controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.

ABSTRACT
The function of transcription in dynamic gene expression programs has been extensively studied, but little is known about how it is integrated with RNA turnover at the genome-wide level. We investigated these questions using the meiotic gene expression program of Schizosaccharomyces pombe. We identified over 80 transcripts that co-purify with the meiotic-specific Meu5p RNA-binding protein. Their levels and half-lives were reduced in meu5 mutants, demonstrating that Meu5p stabilizes its targets. Most Meu5p-bound RNAs were also targets of the Mei4p transcription factor, which induces the transient expression of approximately 500 meiotic genes. Although many Mei4p targets showed sharp expression peaks, Meu5p targets had broad expression profiles. In the absence of meu5, all Mei4p targets were expressed with similar kinetics, indicating that Meu5p alters the global features of the gene expression program. As Mei4p activates meu5 transcription, Mei4p, Meu5p and their common targets form a feed-forward loop, a motif common in transcriptional networks but not studied in the context of mRNA decay. Our data provide insight into the topology of regulatory networks integrating transcriptional and posttranscriptional controls.

Show MeSH
Related in: MedlinePlus