A novel link between Sus1 and the cytoplasmic mRNA decay machinery suggests a broad role in mRNA metabolism

Abstract

BackgroundGene expression is achieved by the coordinated action of multiple factors to ensure a perfect synchrony from chromatin epigenetic regulation through to mRNA export. Sus1 is a conserved mRNA export/transcription factor and is a key player in coupling transcription initiation, elongation and mRNA export. In the nucleus, Sus1 is associated to the transcriptional co-activator SAGA and to the NPC associated complex termed TREX2/THSC. Through these associations, Sus1 mediates the nuclear dynamics of different gene loci and facilitate the export of the new transcripts.ResultsIn this study, we have investigated whether the yeast Sus1 protein is linked to factors involved in mRNA degradation pathways. We provide evidence for genetic interactions between SUS1 and genes coding for components of P-bodies such as PAT1, LSM1, LSM6 and DHH1. We demonstrate that SUS1 deletion is synthetic lethal with 5'→3' decay machinery components LSM1 and PAT1 and has a strong genetic interaction with LSM6 and DHH1. Interestingly, Sus1 overexpression led to an accumulation of Sus1 in cytoplasmic granules, which can co-localise with components of P-bodies and stress granules. In addition, we have identified novel physical interactions between Sus1 and factors associated to P-bodies/stress granules. Finally, absence of LSM1 and PAT1 slightly promotes the Sus1-TREX2 association.ConclusionsIn this study, we found genetic and biochemical association between Sus1 and components responsible for cytoplasmic mRNA metabolism. Moreover, Sus1 accumulates in discrete cytoplasmic granules, which partially co-localise with P-bodies and stress granules under specific conditions. These interactions suggest a role for Sus1 in gene expression during cytoplasmic mRNA metabolism in addition to its nuclear function.

A multi-omics dataset of heat-shock response in the yeast RNA binding protein Mip6

“…Yeast is an ideal research model for transcriptome research because they exhibit most of the cellular complexity present in eukaryotes and have relatively compact, accessible genomes. However, while the interconnected transcriptional circuit has been studied and accepted by many yeast labs 2,[10][11][12][13][14][15] , these studies usually target aspects of the transcriptional regulation and produce separate results that contribute to the overall transcriptional model. Moreover, different strains, experimental conditions and batches are used by different labs and there are few examples of experimental datasets where all these layers have been measured on exactly the same samples.…”

The fate of the messenger is pre-determined: A new model for regulation of gene expression

“…Sus1p, a co-factor of the transcription activator SAGA and the export complex TREX2, genetically and physically interacts with decay factors [81]. Thus, Sus1p may specifically coordinate degradation of SAGA-transcribed, TREX2-exported mRNAs.…”

Stress-specific composition, assembly and kinetics of stress granules in Saccharomyces cerevisiae

“…In theory, newly exported mRNPs could feed directly into non-translating pools such as stress granules or P-bodies and thus could contribute to the different behaviors in assembly and kinetics observed between the granules (Buchan and Parker, 2009;Scarcelli et al, 2008;Cuenca-Bono et al, 2010). Fig.…”