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Spatio-temporal dynamics of yeast mitochondrial biogenesis: transcriptional and post-transcriptional mRNA oscillatory modules.

Lelandais G, Saint-Georges Y, Geneix C, Al-Shikhley L, Dujardin G, Jacq C - PLoS Comput. Biol. (2009)

Bottom Line: This last spatio-temporal module concerns mostly mRNAs coding for basic elements of mitochondrial construction: assembly and regulatory factors.Prediction that unknown genes from this module code for important elements of mitochondrial biogenesis is supported by experimental evidence.More generally, these observations underscore the importance of post-transcriptional processes in mitochondrial biogenesis, highlighting close connections between nuclear transcription and cytoplasmic site-specific translation.

View Article: PubMed Central - PubMed

Affiliation: Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), INSERM UMR-S 665, Université Paris Diderot, Paris, France. gaelle.lelandais@univ-paris-diderot.fr

ABSTRACT
Examples of metabolic rhythms have recently emerged from studies of budding yeast. High density microarray analyses have produced a remarkably detailed picture of cycling gene expression that could be clustered according to metabolic functions. We developed a model-based approach for the decomposition of expression to analyze these data and to identify functional modules which, expressed sequentially and periodically, contribute to the complex and intricate mitochondrial architecture. This approach revealed that mitochondrial spatio-temporal modules are expressed during periodic spikes and specific cellular localizations, which cover the entire oscillatory period. For instance, assembly factors (32 genes) and translation regulators (47 genes) are expressed earlier than the components of the amino-acid synthesis pathways (31 genes). In addition, we could correlate the expression modules identified with particular post-transcriptional properties. Thus, mRNAs of modules expressed "early" are mostly translated in the vicinity of mitochondria under the control of the Puf3p mRNA-binding protein. This last spatio-temporal module concerns mostly mRNAs coding for basic elements of mitochondrial construction: assembly and regulatory factors. Prediction that unknown genes from this module code for important elements of mitochondrial biogenesis is supported by experimental evidence. More generally, these observations underscore the importance of post-transcriptional processes in mitochondrial biogenesis, highlighting close connections between nuclear transcription and cytoplasmic site-specific translation.

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Cluster analysis of nuclear genes involved in mitochondrial                                biogenesis.Periodic gene expression data for yeast grown under continuous,                                nutrient-limited conditions [3] were                                analyzed using the EDPM algorithm. The                                ω-footprints (or                                ω-values) were calculated for each of the                                626 gene expression profiles and used for hierarchical cluster                                analysis (left). Six clusters, A to F, account for the time course                                of periodic expression. They are represented along a time scale from                                the top (cluster A) to the bottom (cluster F). A mean                                    ω-footprint is represented for each                                cluster (middle) and maximal values are indicated by vertical arrows                                together with the number of the associated model pattern.                                Correspondences between maximal                                ω-values and time                                points in the metabolic cycle are indicated by vertical arrows.                                Clusters A to F correspond to distinct phases during the metabolic                                cycle [3]: clusters A and B correspond to                                reductive-building (R/B); clusters C and D, to reductive-charging                                (R/C); and clusters E and F to oxidative activity (Ox). For each of                                the 6 clusters, a set of 10 typical genes is represented (left),                                together with their expression variations.
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pcbi-1000409-g003: Cluster analysis of nuclear genes involved in mitochondrial biogenesis.Periodic gene expression data for yeast grown under continuous, nutrient-limited conditions [3] were analyzed using the EDPM algorithm. The ω-footprints (or ω-values) were calculated for each of the 626 gene expression profiles and used for hierarchical cluster analysis (left). Six clusters, A to F, account for the time course of periodic expression. They are represented along a time scale from the top (cluster A) to the bottom (cluster F). A mean ω-footprint is represented for each cluster (middle) and maximal values are indicated by vertical arrows together with the number of the associated model pattern. Correspondences between maximal ω-values and time points in the metabolic cycle are indicated by vertical arrows. Clusters A to F correspond to distinct phases during the metabolic cycle [3]: clusters A and B correspond to reductive-building (R/B); clusters C and D, to reductive-charging (R/C); and clusters E and F to oxidative activity (Ox). For each of the 6 clusters, a set of 10 typical genes is represented (left), together with their expression variations.

Mentions: The gene clusters presented in the previous section can be distinguished by the model patterns that contribute the most to the EDPM decompositions (see vertical arrows, middle panel Figure 3). The 15 model patterns differ by the time at which they reach their maximal values, so there is a direct relationship between clusters A to F and the temporal phases during metabolic cycle (Figure 4A). For instance, cluster A (262 genes) and B (77 genes) comprised genes whose EDPM decomposition preferentially followed model patterns n°1 and n°2, respectively. The mRNAs of these genes peak at the very beginning of the metabolic cycle (between 0 and 75 minutes). Genes in clusters C (123 genes) and D (27 genes) mainly conformed to model patterns n°5 and 8 and are expressed in the middle of the metabolic cycle (between 75 and 200 minutes). Finally, clusters E (30 genes) and F (107 genes) followed model patterns n°11 and 13 and comprised genes that are expressed at the end of the metabolic cycle (between 200 and 300 minutes).


Spatio-temporal dynamics of yeast mitochondrial biogenesis: transcriptional and post-transcriptional mRNA oscillatory modules.

Lelandais G, Saint-Georges Y, Geneix C, Al-Shikhley L, Dujardin G, Jacq C - PLoS Comput. Biol. (2009)

Cluster analysis of nuclear genes involved in mitochondrial                                biogenesis.Periodic gene expression data for yeast grown under continuous,                                nutrient-limited conditions [3] were                                analyzed using the EDPM algorithm. The                                ω-footprints (or                                ω-values) were calculated for each of the                                626 gene expression profiles and used for hierarchical cluster                                analysis (left). Six clusters, A to F, account for the time course                                of periodic expression. They are represented along a time scale from                                the top (cluster A) to the bottom (cluster F). A mean                                    ω-footprint is represented for each                                cluster (middle) and maximal values are indicated by vertical arrows                                together with the number of the associated model pattern.                                Correspondences between maximal                                ω-values and time                                points in the metabolic cycle are indicated by vertical arrows.                                Clusters A to F correspond to distinct phases during the metabolic                                cycle [3]: clusters A and B correspond to                                reductive-building (R/B); clusters C and D, to reductive-charging                                (R/C); and clusters E and F to oxidative activity (Ox). For each of                                the 6 clusters, a set of 10 typical genes is represented (left),                                together with their expression variations.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2690403&req=5

pcbi-1000409-g003: Cluster analysis of nuclear genes involved in mitochondrial biogenesis.Periodic gene expression data for yeast grown under continuous, nutrient-limited conditions [3] were analyzed using the EDPM algorithm. The ω-footprints (or ω-values) were calculated for each of the 626 gene expression profiles and used for hierarchical cluster analysis (left). Six clusters, A to F, account for the time course of periodic expression. They are represented along a time scale from the top (cluster A) to the bottom (cluster F). A mean ω-footprint is represented for each cluster (middle) and maximal values are indicated by vertical arrows together with the number of the associated model pattern. Correspondences between maximal ω-values and time points in the metabolic cycle are indicated by vertical arrows. Clusters A to F correspond to distinct phases during the metabolic cycle [3]: clusters A and B correspond to reductive-building (R/B); clusters C and D, to reductive-charging (R/C); and clusters E and F to oxidative activity (Ox). For each of the 6 clusters, a set of 10 typical genes is represented (left), together with their expression variations.
Mentions: The gene clusters presented in the previous section can be distinguished by the model patterns that contribute the most to the EDPM decompositions (see vertical arrows, middle panel Figure 3). The 15 model patterns differ by the time at which they reach their maximal values, so there is a direct relationship between clusters A to F and the temporal phases during metabolic cycle (Figure 4A). For instance, cluster A (262 genes) and B (77 genes) comprised genes whose EDPM decomposition preferentially followed model patterns n°1 and n°2, respectively. The mRNAs of these genes peak at the very beginning of the metabolic cycle (between 0 and 75 minutes). Genes in clusters C (123 genes) and D (27 genes) mainly conformed to model patterns n°5 and 8 and are expressed in the middle of the metabolic cycle (between 75 and 200 minutes). Finally, clusters E (30 genes) and F (107 genes) followed model patterns n°11 and 13 and comprised genes that are expressed at the end of the metabolic cycle (between 200 and 300 minutes).

Bottom Line: This last spatio-temporal module concerns mostly mRNAs coding for basic elements of mitochondrial construction: assembly and regulatory factors.Prediction that unknown genes from this module code for important elements of mitochondrial biogenesis is supported by experimental evidence.More generally, these observations underscore the importance of post-transcriptional processes in mitochondrial biogenesis, highlighting close connections between nuclear transcription and cytoplasmic site-specific translation.

View Article: PubMed Central - PubMed

Affiliation: Dynamique des Structures et Interactions des Macromolécules Biologiques (DSIMB), INSERM UMR-S 665, Université Paris Diderot, Paris, France. gaelle.lelandais@univ-paris-diderot.fr

ABSTRACT
Examples of metabolic rhythms have recently emerged from studies of budding yeast. High density microarray analyses have produced a remarkably detailed picture of cycling gene expression that could be clustered according to metabolic functions. We developed a model-based approach for the decomposition of expression to analyze these data and to identify functional modules which, expressed sequentially and periodically, contribute to the complex and intricate mitochondrial architecture. This approach revealed that mitochondrial spatio-temporal modules are expressed during periodic spikes and specific cellular localizations, which cover the entire oscillatory period. For instance, assembly factors (32 genes) and translation regulators (47 genes) are expressed earlier than the components of the amino-acid synthesis pathways (31 genes). In addition, we could correlate the expression modules identified with particular post-transcriptional properties. Thus, mRNAs of modules expressed "early" are mostly translated in the vicinity of mitochondria under the control of the Puf3p mRNA-binding protein. This last spatio-temporal module concerns mostly mRNAs coding for basic elements of mitochondrial construction: assembly and regulatory factors. Prediction that unknown genes from this module code for important elements of mitochondrial biogenesis is supported by experimental evidence. More generally, these observations underscore the importance of post-transcriptional processes in mitochondrial biogenesis, highlighting close connections between nuclear transcription and cytoplasmic site-specific translation.

Show MeSH