Pbp1 Is Involved in Ccr4- and Khd1-Mediated Regulation of Cell Growth through Association with Ribosomal Proteins Rpl12a and Rpl12b

Abstract

The Saccharomyces cerevisiae Pbp1 [poly(A)-binding protein (Pab1)-binding protein] is believed to be involved in RNA metabolism and regulation of translation, since Pbp1 regulates a length of poly(A) tail and is involved in stress granule (SG) formation. However, a physiological function of Pbp1 remains unclear, since the pbp1⌬ mutation has no obvious effect on cell growth. In this study, we showed that PBP1 genetically interacts with CCR4 and KHD1, which encode a cytoplasmic deadenylase and an RNA-binding protein, respectively. Ccr4 and Khd1 modulate a signal from Rho1 in the cell wall integrity pathway by regulating the expression of RhoGEF and RhoGAP, and the double deletion of CCR4 and KHD1 confers a severe growth defect displaying cell lysis. We found that the pbp1⌬ mutation suppressed the growth defect caused by the ccr4⌬ khd1⌬ mutation. The pbp1⌬ mutation also suppressed the growth defect caused by double deletion of POP2, encoding another cytoplasmic deadenylase, and KHD1. Deletion of the gene encoding previously known Pbp1-interacting factor Lsm12, Pbp4, or Mkt1 did not suppress the growth defect of the ccr4⌬ khd1⌬ mutant, suggesting that Pbp1 acts independently of these factors in this process. We then screened novel Pbp1-interacting factors and found that Pbp1 interacts with ribosomal proteins Rpl12a and Rpl12b. Similarly to the pbp1⌬ mutation, the rpl12a⌬ and rpl12b⌬ mutations also suppressed the growth defect caused by the ccr4⌬ khd1⌬ mutation. Our results suggest that Pbp1 is involved in the Ccr4-and Khd1-mediated regulation of cell growth through the association with Rpl12a and Rpl12b.

Mammalian ataxin-2 modulates translation control at the pre-initiation complex via PI3K/mTOR and is induced by starvation

“…The yeast ortholog of ATXN2, Pbp1, is also an interactor of poly(A) binding protein and modulates RNA processing, relocalizing to SG in periods of cell stress [38, 39]. Recent reports showed a role of Pbp1 in the regulation of mTOR signals that control translation [40, 41] and implicated it in the stress-dependent translational regulation of precursor proteins destined to mitochondria [42].…”

Regulation of LRG1 expression by RNA‐binding protein Puf5 in the budding yeast cell wall integrity pathway

“…pbp1 mutation is dependent on another deadenylase, Pan2. A previous report also showed that pbp1Δ suppresses the temperature-sensitive phenotype associated with ccr4Δ mutant (Kimura et al, 2013). Thus, we examined whether pbp1Δ affects the growth defect of puf5Δ at high temperature.…”

The Aspergillus nidulans Pbp1 homolog is required for normal sexual development and secondary metabolism

“…Further studies have shown deletions of pbp1 to suppress defects and or/lethality associated with mutations of other key genes (Kimura and Irie, 2013; Mangus et al, 1998; Woolstencroft et al, 2006). This is particularly interesting in light of the lack of severe phenotypes seen in pbp1 mutants (Kimura and Irie, 2013).…”

“…Further studies have shown deletions of pbp1 to suppress defects and or/lethality associated with mutations of other key genes (Kimura and Irie, 2013; Mangus et al, 1998; Woolstencroft et al, 2006). This is particularly interesting in light of the lack of severe phenotypes seen in pbp1 mutants (Kimura and Irie, 2013). Given Pbp1’s role in regulating HO translation (Tadauchi et al, 2004), and pheromone production (Park et al, 2016), it is a formal possibility that PbpA is required for proper expression and/or translation of mating type ( MAT ) genes.…”

“…Deletion of PBP1 in S. cerevisiae leads to significant decreases in stress granule formation under glucose deprivation, while P-bodies are unaffected. In line with its role in stress granule assembly, PBP1 has also been implicated in resistance to various stresses, including caffeine, cycloheximide, hydroxyurea (Kapitzky et al, 2010), and recovery from ethanol stress (Kato et al, 2011), as well as regulation of poly-A tail length (Mangus et al, 1998; Mangus et al, 2004), and cell growth (Kimura and Irie, 2013). Here we show that AN1325 , here called pbpA , is a homolog of yeast PBP1 and is required for normal sexual sporulation and has a repressive effect on secondary metabolism but has no major role in either P-body or stress granule biology in A. nidulans .…”