High impact information on MFA2

• In addition, in cells deleted for the XRN1 gene, which encodes a major 5' to 3' exonuclease in yeast, the MFA2 transcript is deadenylated normally but persists as a full-length mRNA lacking the 5' cap structure [1].
• Analysis of point mutations obtained from this screen, and of additional lesions constructed in vitro, indicated that the MFA2 3'-untranslated region (UTR) contains sequences that specify rapid mRNA decay [2].
• Poly(A) shortening rates are stimulated by the yeast a-mating factor (MFA2) RNA 3' UTR sequence, and this occurs by switching PAN from a distributive to a more processive enzyme [3].
• UV-related histone hyperacetylation and chromatin remodeling in the MFA2 promoter depend on Gcn5p and partially on Swi2p, respectively [4].
• Deletion of GCN5, but not of SWI2, impairs repair of DNA damage in the MFA2 promoter [4].

Biological context of MFA2

• Two a-factor structural genes, MFA1 and MFA2, have been previously cloned with synthetic probes based on the a-factor amino acid sequence (A. Brake, C. Brenner, R. Najarian, P. Laybourn, and J. Merryweather, cited in M.-J. Gething [ed.], Protein transport and secretion, 1985) [5].
• In this study, the effect of a prior UV irradiation on the removal of cyclobutane pyrimidine dimers (CPDs) from the transcribed strand (TS) and non-transcribed strand (NTS) of the MFA2 gene in haploid Saccharomyces cerevisiae (S. cerevisiae) cells was investigated [6].
• How transcription-coupled (TCR) and global genome repair (GGR) operate at the transcriptionally active and/or repressed S. cerevisiae MFA2 locus, and how this relates to nucleosome positioning are considered [7].
• The effect of Gcn5p's absence in reducing NER was local and UV stimulates Gcn5p-mediated histone acetylation at the repressed MFA2 promoter [7].
• The system developed permits further dissection of the relationships between DNA repair, chromatin structure and transcription at the MFA2 locus [8].

Associations of MFA2 with chemical compounds

• The Saccharomyces cerevisiae histone acetyltransferase Gcn5 has a role in the photoreactivation and nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers in the MFA2 gene [9].
• The deletion of GCN5 markedly reduced the PR and NER of UV-induced cyclobutane pyrimidine dimers in MFA2 but much less so in RPB2, whereas no detectable defect was seen for repair of the genome overall [9].
• DMS chemical probing of A and C nucleotides of intracellular MFA2 mRNA was then done [10].
• In contrast, inhibition of translation in trans, by the addition of cycloheximide, stabilized the deadenylated form of MFA2 mRNA [11].
• The spectra of enzyme-sensitive sites and single-strand breaks induced by MB in vitro or by RO plus light in vivo or in vitro were examined in two yeast reporter genes: the nuclear MFA2 and the mitochondrial OLI1 [12].

Physical interactions of MFA2

• We find that Pab1p can bind the MFA2 3'-UTR in a regulated manner to control MFA2 3'-UTR reporter translation [13].
• Pub1p binds the MFA2 3'-UTR in a p38 MAPK/Hog1p-regulated manner in response to carbon source growth conditions [13].
• MFA2 is specifically stabilized in a strain bearing a temperature-sensitive mutation in the SSA1 gene [14].

Regulatory relationships of MFA2

• p38 mitogen-activated protein kinase/Hog1p regulates translation of the AU-rich-element-bearing MFA2 transcript [13].

Other interactions of MFA2

• We employed the MFA2 and MET16 genes as models [7].
• After UV irradiation Swi2p is partly responsible for facilitating access to restriction of DNA in the cores of the nucleosomes at the MFA2 promoter [7].
• In Delta(gcn5), the MFA2 mRNA level is reduced by fourfold, while transcription from RPB2 is reduced only to 80 % [9].
• The approach also revealed that RAD16 has a role in the repair of the TS when MFA2 is active [8].
• The post-UV histone modifications and chromatin remodeling at the repressed MFA2 promoter do not activate MFA2 transcriptionally, nor do they require damage recognition by Rad4p or Rad14p [4].

Analytical, diagnostic and therapeutic context of MFA2

• Chromatin immunoprecipitation with anti-acetyl histone H3 (K9 and K14) and anti-acetyl histone H4 (K5, K8, K12, and K16) antibodies shows that Lys-9 and/or Lys-14 of histone H3, but not the relevant sites of histone H4 in nucleosomes at the repressed MFA2 promoter, are hyperacetylated after UV irradiation [4].
• We confirmed repair trends seen using Southern blotting to examine kilobase size fragments, but were additionally able to elucidate subtle differences in repairing portions of the transcribed strand (TS) of MFA2 [8].

References