Disease relevance of ASH1

• Constitutively expressing an ASH1 mRNA containing the bacteriophage MS2 coat-protein binding site adjacent to the ASH1 3' UTR allowed us to visualize ASH1 mRNA with an MS2-coat-protein-GFP fusion protein (together denoted 'gRNAASH1') [1].
• Finally, we show that ASH1 is required for full virulence of C. albicans in a mouse model of disseminated candidiasis [2].

High impact information on ASH1

• Formation of the ASH1 mRNP requires recognition of zip code elements by the RNA binding protein She2p [3].
• Actin-dependent transport of ASH1 mRNA in yeast represents one of the best-characterized examples of mRNP translocation [3].
• Using CHIP, we measured recruitment of Swi/Snf, SAGA, the repressor Ash1p, and transcription factors Swi5p and SBF to the HO endonuclease promoter as cells progress through the yeast cell cycle [4].
• ASH1 encodes a zinc finger protein whose preferential accumulation in daughter cell nuclei at the end of anaphase depends on She1p/Myo4p [5].
• Asymmetric accumulation of Ash1p in postanaphase nuclei depends on a myosin and restricts yeast mating-type switching to mother cells [5].

Biological context of ASH1

• A new yeast PUF family protein, Puf6p, represses ASH1 mRNA translation and is required for its localization [6].
• Puf6p-bound PUF consensus sequences in the 3'UTR of ASH1 mRNA and repressed the translation of ASH1 mRNA both in vivo and in vitro [6].
• The localization of ASH1 mRNA to the distal tip of budding yeast cells is essential for the proper regulation of mating type switching in Saccharomyces cerevisiae [7].
• These data suggest that phosphorylation of Ash1 by Pho85 governs stability of Ash1 protein [8].
• Therefore, the ASH1 3'UTR-dependent particle serves as a marker for RNA transport and localization [9].

Anatomical context of ASH1

• Mother cells, in contrast, contain little or no Ash1 and thus are able to transcribe HO [8].
• To achieve this localization, Ash1 mRNA must have its 3' untranslated region and the actin cytoskeleton must be intact [10].

Physical interactions of ASH1

• Here we show that She2p is a novel RNA-binding protein that binds specifically to ASH1 mRNA in vivo and to ASH1 RNA zip codes in vitro [11].

Regulatory relationships of ASH1

• Thus, Ash1p is a cell fate determinant that is asymmetrically localized to the daughter nucleus where it inhibits HO transcription [12].
• Our epistasis analyses are consistent with the deduction that Ash1 acts separately from the mitogen-activated protein kinase cascade and Ste12 [13].

Other interactions of ASH1

• A mutant She2 protein that is unable to recognize its cognate target mRNA, ASH1, fails to localize Myo4p [14].
• She2p can interact with She3 protein via She3p's C-terminus and becomes localized to the daughter cell tip upon ASH1 expression [11].
• In pho85 mutants, Ash1 protein is no longer asymmetrically localized and is present, instead, in both mother and daughter cells [8].
• We describe a gene, ASH1, that is necessary to repress HO in daughters [5].
• In budding yeast, ASH1 mRNA is translocated via actin and myosin to the tip of growing cells [15].

Analytical, diagnostic and therapeutic context of ASH1

• Co-immunoprecipitation studies also indicated that Khd1 associates with ASH1 mRNA through the N element [16].
• A GFP-decorated reporter transcript containing the ASH1 3' untranslated region gRNA(ASH1) forms spots of fluorescence localized to a cortical domain at the bud tip, relocates to the mother-bud neck before cell separation, and finally migrates to the incipient bud site before the next budding cycle [15].

References