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.
Highlights
Gene expression is achieved by the coordinated action of multiple factors to ensure a perfect synchrony from chromatin epigenetic regulation through to mRNA export
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
Sus1 interacts genetically with components of the mRNA degradation machinery Unveiling the network of genetic interactions for a given factor provides clues to understand its role in a cellular context
Summary
Gene expression is achieved by the coordinated action of multiple factors to ensure a perfect synchrony from chromatin epigenetic regulation through to mRNA export. Sus is associated to the transcriptional co-activator SAGA and to the NPC associated complex termed TREX2/THSC Through these associations, Sus mediates the nuclear dynamics of different gene loci and facilitate the export of the new transcripts. The coordinated action of several multiprotein complexes couple transcription, mRNA biogenesis and export, to guarantee the proper maturation of transcripts before their translation in the cytoplasm [1]. Study of stress granule formation has suggested that they contain mRNAs stalled in the process of translation initiation. In yeast they characteristically contain poly(A) mRNA, the poly (A)-binding protein Pab1, 40S ribosomal subunits and the translation factors eIF4E, eIF4G, eIF3 (reviewed in [4,5])
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