Disease relevance of PAB1

• A nonspecific single-stranded binding protein from Escherichia coli did not restore stability to polyadenylated mRNA, and the stabilizing effect of PABP was inhibited by anti-PABP antibody [1].
• Plants that accumulate the Pab1p display a range of abnormalities, ranging from a characteristic chlorosis in leaves to a necrosis and large inhibition of growth [2].

High impact information on PAB1

• A 55 residue A-rich region upstream of the initiator methionine codon in the mRNA shows an affinity for poly(A)-binding protein comparable to that of poly(A)180-220, raising the possibility of feedback regulation of translation [3].
• The aberrant production of 25S ribosomal RNA (rRNA) occurring in spb4-1 mutants or the deletion of SPB2 (RPL46) permits the deletion of PAB1 [4].
• Yeast poly(A)-binding protein, Pab1, and PAN, a poly(A) nuclease complex recruited by Pab1, connect mRNA biogenesis to export [5].
• Pab1 contains a nonessential leucine-rich nuclear export signal and shuttles between the nucleus and the cytoplasm [5].
• In vivo, the tail interacts with a conserved polypeptide, poly(A) binding protein (Pab1p) [6].

Biological context of PAB1

• Deletion of the PAT1 gene affects translation initiation and suppresses a PAB1 gene deletion in yeast [7].
• Second, overexpression of PAB1 does not cure the [PSI(+)] phenotype or solubilize detectable amounts of eRF3 [8].
• Previous studies have implicated the cytoplasmic poly(A) tail-binding protein Pab1p in poly(A) tail length control during polyadenylation [9].
• Here, we identify Nab2p as a nuclear poly(A)-binding protein required for both poly(A) tail length control and nuclear export of mRNA [9].
• The suppression of pab1Delta by pbp1Delta appears to be different from that mediated by other pab1 suppressors, since disruption of PBP1 does not alter translation rates, affect accumulation of ribosomal subunits, change mRNA poly(A) tail lengths, or result in a defect in mRNA decay [10].

Anatomical context of PAB1

• We determined that a fraction of Pbp1p cosediments with polysomes in sucrose gradients and that its distribution is very similar to that of Pab1p [10].
• The yeast hsp70 homologue Ssa is required for translation and interacts with Sis1 and Pab1 on translating ribosomes [11].
• Pab1p was found to associate with purified COPI-coated vesicles generated from Golgi membranes in vitro [12].
• Furthermore, substituting PAB3 for the yeast Pab1p caused synthetic lethality with rna15-2 and gle2-1, alleles of the genes that encode a component of the nuclear pre-mRNA cleavage factor I, and a factor associated with the nuclear pore complex, respectively [13].
• In this report, we have analyzed the effects of overexpressing PABP on the regulation of mRNAs during Xenopus oocyte maturation [14].

Associations of PAB1 with chemical compounds

• Yeast mRNA Poly(A) tail length control can be reconstituted in vitro in the absence of Pab1p-dependent Poly(A) nuclease activity [15].
• Yeast pab1 mutants were found to be sensitive to elevated concentrations of copper (Cu) and 3-aminotriazole (3-AT) in the growth medium [16].
• This is 50 times more than required to bind all the poly(A) in the egg based on the binding stoichiometry of 1 PABP per 27 adenosine residues [17].
• Both poly(A)(+) transcripts and/or Pab1p can be detected in P-bodies during glucose deprivation and in stationary phase [18].

Physical interactions of PAB1

• Rbp29p can be co-immunoprecipitated with the poly(A) tail-binding protein Pab1p from crude yeast extracts in a dosage- and RNA-dependent manner [19].
• We suggest a model in which these three factors and Ufd1p are part of a regulatory complex that exploits Pab1p to link cleavage and polyadenylation factors of CFIA and CFIB (cleavage factors IA and IB) to the polyadenylation factors of CPF (cleavage and polyadenylation factor) [20].
• These data suggest that eIF4G mediates poly(A) tail stimulated translation in vitro, and that Pab1p and the domain encompassing the Pab1p-binding site on eIF4G can compensate for partial loss of eIF4E function in vivo [21].
• However, the domains required for Pan3p and Pbp1p binding on Pab1p are distinct [22].
• Yeast Pab1 interacts with Rna15 and participates in the control of the poly(A) tail length in vitro [23].

Regulatory relationships of PAB1

• These effects suggest that Pbp1p may act to repress the ability of Pab1p to negatively regulate polyadenylation [10].
• Furthermore, the inviability of a pab1 deletion strain is suppressed by a mutation in the 5'-3' exoribonuclease RRP6, a component of the nuclear exosome [24].
• We confirmed that a genetic interaction exists between eRF3 and Pab1p and showed that Pab1p overexpression enhances the efficiency of termination in SUP35 (eRF3) mutant and [PSI(+)] cells [8].
• This suggests that serum stimulates the interaction between eIF4G and PABP by a distinct mechanism that is independent of both the mTOR pathway and the enhanced association of eIF4G with eIF4E [25].

Other interactions of PAB1

• Disruption of PBP1 showed that it is not essential for viability but can suppress the lethality associated with a PAB1 deletion [10].
• The yeast Pan2 protein is required for poly(A)-binding protein-stimulated poly(A)-nuclease activity [26].
• Pab1 shuttles rapidly between the nucleus and the cytoplasm and partially accumulates in the nucleus when the function of Xpo1/Crm1 is inhibited [24].
• RNase mapping of transcripts from pap1-1 cells revealed PAB1 mRNA to be poly(A)- whereas TCM1 exists as equal amounts of poly(A)- and poly(A)+ mRNA 60 min after shift [27].
• These data confirm that Pan2p and not Pan1p is required for PAN activity, and they suggest that ribonucleases other than the Pab1p-stimulated PAN are capable of shortening poly(A) tails in vivo [26].

Analytical, diagnostic and therapeutic context of PAB1

• Indirect cellular immunofluorescence combined with digital image processing allowed a detailed comparison of the intracellular distributions of PUB1 and PAB1 [28].
• We found that Pab1 interacts with Rna15 in two-hybrid assays and in coimmunoprecipitation experiments [23].
• Hybridization screening of genomic and cDNA libraries with a genomic PCR probe led to the isolation of three diverse Arabidopsis genes encoding PABPs, PAB1, PAB3, and PAB5 [29].
• Here, we demonstrate the reconstitution of an eIF4E/eIF4G/Pab1p complex with recombinant proteins, and show by atomic force microscopy that the complex can circularize capped, polyadenylated RNA [30].
• Although mRNA export is clearly not a default option, neither inhibition of protein synthesis, inhibition of mRNA splicing, nor inhibition of poly(A)-binding protein function blocks export of the average poly(A)+, as judged by in situ hybridization [31].

References