The exonuclease xrn1: a key regulator of gene expression under physiological and perturbed conditions
- Autores: Leire de Campos Mata
- Directores de la Tesis: Juana Díez Antón (dir. tes.), Jennifer Jungfleisch (codir. tes.)
- Lectura: En la Universitat Pompeu Fabra ( España ) en 2019
- Idioma: español
- Tribunal Calificador de la Tesis: Eulàlia de Nadal Clanchet (presid.), Oriol Gallego Moli (secret.), Sebastián Chávez de Diego (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Pompeu Fabra
- Materias:
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- Resumen
Gene expression is a fundamental process in cell cycle. Genes encode for proteins and other functional gene products that will determine the fate of a cell. Each step in the flow of information from DNA to RNA and from RNA to protein represents a layer of cell self-regulation of its functions. Although classical biology considered them as isolated steps, recent research has revealed that transcription, translation and degradation are interconnected and regulated by shared elements. These include the RNA polymerase II subunits Rpb4 and Rpb7 which shuttle between the nucleus and the cytoplasm to aid in all steps of gene expression. Similarly, the translation initiation factor eIF4G is imported to the nucleus to act in splicing thereby intertwining transcription and translation. Another example that bridges nuclear and cytoplasmic events is the exonuclease Xrn1 that regulates mRNA homeostasis by promoting transcription and degradation of cellular mRNAs.
Precise tuning of gene expression is of major importance to ensure adaptation and survival of cells when faced with suboptimal environmental conditions. Under stress, cell-growth related genes are shut down and expression of stress-protective genes is favored by the interconnection of several stress-activated signaling pathways. Xrn1 has been shown to play an essential role under glucose deprivation by maintaining mRNA homeostasis of adenosine monophosphate-activated protein kinase Snf1-dependent genes.
In this thesis we characterize the role of the exonuclease Xrn1 as a major regulator of gene expression by coupling degradation, transcription and translation of a subset of mRNAs with shared features. In addition, we reveal that Xrn1 modulates transcriptional and translational responses upon hyper-osmotic shock in a yeast model system. These results place Xrn1 at the crossroads of transcription, translation and degradation, the three major stages of gene expression and furthermore show the importance of Xrn1 under perturbed environmental conditions.
