High impact information on RIM101

• In the homologous system in Saccharomyces cerevisiae, the zinc-finger transcription factor Rim101 is activated under alkaline conditions to regulate transcription of target genes [1].
• We have found that the ability of Rim101 to be proteolytically processed to its active form and mediate NRE-directed repression not only depends on the previously characterized RIM signaling pathway but also requires Dfg16, Ygr122w, and components of the ESCRT trafficking pathway [2].
• We show that Nrg1 and Rim101 bind simultaneously to adjacent target sites within the NRE in vitro and act as corepressors in vivo [2].
• Interestingly, Rim101 was processed in bro1 and doa4 strains but was unable to mediate efficient repression [2].
• A reporter gene containing deduced Rim101p binding sites is negatively regulated by Rim101p and is associated with Rim101p in vivo [3].

Biological context of RIM101

• The ability to respond to neutral-to-alkaline pHs is governed in part by the RIM101 signal transduction pathway [4].
• Because Rim101p activates ion pump genes, we tested the role of RIM101 in ion homeostasis and found that RIM101 promotes resistance to elevated cation concentrations [5].
• A study in the context of trans-regulatory mutations in the Y. lipolytica RIM101 gene showed that the PacC-like sites, potential binding sites for YlRim101p, were implicated in the derepression of UAS2-driven expression at neutral-alkaline pH [6].
• The relationship between the MVB pathway and Rim101p pathway is conserved in Candida albicans, because mutations in four ESCRT subunit genes abolish alkaline pH-induced filamentation, a phenotype previously seen for rim101 and rim20 mutants [7].
• The extragenic suppressors in two independent revertants were identified as nonsense mutations in the pH response regulator RIM101 (PRR2) that resulted in a carboxy-terminal truncation of the open reading frame [8].

Anatomical context of RIM101

• Therefore, the absence of a functional RIM101 pathway leads to cell wall defects. rim21Delta, as well as rim101Delta, was synthetic lethal with slt2Delta, a synthetic defect alleviated by osmotic stabilization of the media [9].
• These results suggest that Snf7p may serve two functions in the cell: one as a RIM101 pathway member and one for MVB transport to the vacuole [10].

Associations of RIM101 with chemical compounds

• Further, our studies suggest that the RIM101 pathway promotes pH-independent responses, including resistance to high concentrations of lithium and to the drug hygromycin B [4].
• These results indicate that a calpain-like cysteine protease, Cpl1p, plays an important role in alkaline adaptation and sporulation processes, via regulation of the turnover and processing of the transcription factor Rim101p [11].
• At one site, substitution of alanine for serine does not affect RIM1 activity; at the other site, this substitution impairs activity [12].

Regulatory relationships of RIM101

• Expression of a Rim1p C-terminal deletion derivative suppresses rim8, 9, and 13 mutations [13].
• Disruption of CPL1 also causes reduced sporulation efficiency and promotes the degradation of the transcription factor Rim101p, which is involved in the sporulation pathway and has been shown to accumulate in a C-terminally truncated, active form under alkaline conditions [11].

Other interactions of RIM101

• We find that Rim20-GFP foci accumulate in a vps4 mutant background independently of external pH, Rim101 pathway-specific genes, and most ESCRT subunit genes except for SNF7 [14].
• Candida albicans Rim13p, a protease required for Rim101p processing at acidic and alkaline pHs [4].
• We propose that alkaline growth conditions alter the endosomal surface to favor Rim20-Snf7 interaction and Rim101 cleavage [14].
• In this report, we have determined the relationship between RIM1 and the other genes, RIM8, 9, and 13, in this group [13].
• In the yeast Saccharomyces cerevisiae, rim1, 8, 9, or 13 mutations cause four phenotypes: poor growth at low temperature, altered colony morphology, inefficient sporulation due to reduced expression of the meiotic activator IME1, and, as shown here, defective invasive growth [13].

Analytical, diagnostic and therapeutic context of RIM101

• Chromatin immunoprecipitation assays show that Rim101p is associated in vivo with the promoters of seven Rim101p-repressed genes [3].
• Microarray analysis of rim101-/- cells indicated that Rim101p does not govern transcriptional responses at acidic pH, but does regulate a subset of transcriptional responses at alkaline pH, including the iron acquisition genes [15].

References