MitoGenesisDB: Mitochondrial Spatio-Temporal Expression Database

REFERENCES

1. Saint-Georges Y., Garcia M., Delaveau T., Jourdren L., Le Crom S., Lemoine S., Tanty V., Devaux F. and Jacq C., 2008.
Yeast mitochondrial biogenesis: a role for the PUF RNA-binding protein Puf3p in mRNA localization.
PLoS ONE 3: e2293 [Pubmed]

Summary: The asymmetric localization of mRNA plays an important role in coordinating posttranscriptional events in eukaryotic cells. We investigated the peripheral mitochondrial localization of nuclear-encoded mRNAs (MLR) in various conditions in which the mRNA binding protein context and the translation efficiency were altered. We identified Puf3p, a Pumilio family RNA-binding protein, as the first trans-acting factor controlling the MLR phenomenon. This allowed the characterization of two classes of genes whose mRNAs are translated to the vicinity of mitochondria. Class I mRNAs (256 genes) have a Puf3p binding motif in their 3'UTR region and many of them have their MLR properties deeply affected by PUF3 deletion. Conversely, mutations in the Puf3p binding motif alter the mitochondrial localization of BCS1 mRNA. Class II mRNAs (224 genes) have no Puf3p binding site and their asymmetric localization is not affected by the absence of PUF3. In agreement with a co-translational import process, we observed that the presence of puromycin loosens the interactions between most of the MLR-mRNAs and mitochondria. Unexpectedly, cycloheximide, supposed to solidify translational complexes, turned out to destabilize a class of mRNA-mitochondria interactions. Classes I and II mRNAs, which are therefore transported to the mitochondria through different pathways, correlated with different functional modules. Indeed, Class I genes code principally for the assembly factors of respiratory chain complexes and the mitochondrial translation machinery (ribosomes and translation regulators). Class II genes encode proteins of the respiratory chain or proteins involved in metabolic pathways. Thus, MLR, which is intimately linked to translation control, and the activity of mRNA-binding proteins like Puf3p, may provide the conditions for a fine spatiotemporal control of mitochondrial protein import and mitochondrial protein complex assembly. This work therefore provides new openings for the global study of mitochondria biogenesis.

2. Tu B. P., Kudlicki A., Rowicka M. and McKnight S. L., 2005.
Logic of the yeast metabolic cycle: temporal compartimentalization of cellular processes.
Science 310: 1152-115 [Pubmed]

Summary: Budding yeast grown under continuous, nutrient-limited conditions exhibit robust, highly periodic cycles in the form of respiratory bursts. Microarray studies reveal that over half of the yeast genome is expressed periodically during these metabolic cycles. Genes encoding proteins having a common function exhibit similar temporal expression patterns, and genes specifying functions associated with energy and metabolism tend to be expressed with exceptionally robust periodicity. Essential cellular and metabolic events occur in synchrony with the metabolic cycle, demonstrating that key processes in a simple eukaryotic cell are compartmentalized in time.

3. Lelandais G., Saint-Georges Y., Geneix C., Al-Shikhley L., Dujardin G and Jacq C., 2009.
Spatio-temporal dynamics of yeast mitochondrial biogenesis: transcriptional and post-transcriptional mRNA oscillatory modules.
PLoS Comput Biol 5: e1000409 [Pubmed]

Summary: 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.

4. Garcia-Martinez J., Aranda A. and Perez-Ortin J. E., 2004.
Genomic run-on evaluates transcription rates for all yeast genes and identifies gene regulatory mechanisms.
Mol Cell 15: 303-313 [Pubmed]

Summary: Most studies of eukaryotic gene regulation have been done looking at mature mRNA levels. Nevertheless, the steady-state mRNA level is the result of two opposing factors: transcription rate (TR) and mRNA degradation. Both can be important points to regulate gene expression. Here we show a new method that combines the use of nylon macroarrays and in vivo radioactive labeling of nascent RNA to quantify TRs, mRNA levels, and mRNA stabilities for all the S. cerevisiae genes. We found that during the shift from glucose to galactose, most genes undergo drastic changes in TR and mRNA stability. However, changes in mRNA levels are less pronounced. Some genes, such as those encoding mitochondrial proteins, are coordinately regulated in mRNA stability behaving as decay regulons. These results indicate that, although TR is the main determinant of mRNA abundance in yeast, modulation of mRNA stability is a key factor for gene regulation.