Role of Upf1 and Csx1 in posttranscriptional regulation of gene expression in Schizosaccharomyces Pombe

Resumen

Eukaryotic cells have developed a complex regulatory system in order to adapt to different environmental and cellular requirements. RNA binding proteins (RBPs) modify and specifically regulate mRNA localization, function, stability and biogenesis. Thus, changes in the RBPs can promote diseases derived of mRNA missregulation. Using Schizosaccharomyces pombe as model organism we have studied the role of the RBPs Upf1 and Csx1 in posttranscriptional regulation of gene expression. As a result we have found that Upf1 is binding a large amount of mRNAs which carry out different cellular functions. Throughout DNA microarrays experiments we have observed that Upf1 could be degrading these mRNAs. This implies a novel finding because in previous reports it has been described that Upf1 is usually degrading mRNAs that contain premature termination codons (PTCs) while our experiments reveals that Upf1 could be degrading transcripts without evident PTCs. Besides, we have demonstrated that other components of the non-sense mediated mRNA decay (NMD), such as Upf2 or Upf3, are required for Upf1- mRNA targets binding. It has also been demonstrated that the interaction between Upf1 and Upf2, reported in other organisms is conserved in fission yeast, being the presence of Upf2 required for a proper Upf1 intracellular localization. Previous reports have described that Upf1 is necessary for the oxidative stress response. In this work it has been proposed that the role of Upf1 in this response could be mediated by the degradation of some of its targets. In this work it has been established the hypothesis that NMD mechanism could be taking place during transcription and translation due to the results obtained through the study of protein interactions in vivo. In addition it has been demonstrated that UPF1 dimerizes in mammalian cells. Finally, it has been proved that Csx1 is playing a regulator role in the sexual differentiation response through the binding and regulation of abundance of ste11+ mRNA. This finding and the previous reports establish that Csx1 is a key component of two cellular responses, being a candidate for the cross-talk between both pathways.