Disease relevance of Pabpc2

• We report that infection of MT-2 cells with HIV-1 leads to efficient proteolysis of PABP [1].
• Cleavage of PABP by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis [1].
• Purified HIV-1 and HIV-2 proteases cleave PABP1 directly at positions 237 and 477, separating the two first RNA-recognition motifs from the C-terminal domain of PABP [1].
• These findings indicate that some retroviruses may share with picornaviruses and caliciviruses the capacity to proteolyse PABP [1].

High impact information on Pabpc2

• Poly(A)-binding protein (PABP) is an important regulator of gene expression that has been implicated in control of translation initiation [2].
• Furthermore, transfection experiments show that the first 32 nucleotides of PABP mRNA are sufficient to confer growth-dependent translational control on a heterologous mRNA [2].
• First, the promoter of the Pabp2 gene is not derived from its intron-containing progenitor, Pabp1 [3].
• The gene encoding the testis-specific isoform of mouse poly(A) binding protein (Pabp2) has been isolated and sequenced [3].
• Second, mRNAs encoding somatic PABP isoform, PABP1, are present at high levels in meiotic and haploid spermatogenic cells [3].

Biological context of Pabpc2

• The mouse gene encoding the testis-specific isoform of Poly(A) binding protein (Pabp2) is an expressed retroposon: intimations that gene expression in spermatogenic cells facilitates the creation of new genes [3].
• Thus, the mouse Pabp2 gene is a retroposon, created by synthesizing a reverse transcriptase copy of a processed mRNA and inserting the copy into the genome [3].
• Unexpectedly, comparison of the sequence of genomic and cDNAs demonstrated that the Pabp2 gene lacks introns, whereas all other functional Pabp genes in plants, amphibians, and mammals contain introns [3].
• In the present study, we have determined the transcription start site of the Pabp2 gene to clarify the source of its promoter, a prerequisite for expression of retroposons and preservation of their function by natural selection [4].
• Transfection experiments with chimeric constructs suggest that the lack of translational autoregulation of endogenous PABP mRNA in these cells appears to reflect the presence of an overriding regulatory element outside the A-rich region [5].

Anatomical context of Pabpc2

• Thus, overexpression of PABP in mouse NIH 3T3 fibroblasts represses the translation of the respective endogenous mRNA or that of a chimeric mRNA containing just the 5' UTR of PABP mRNA [5].
• Two PABP cDNAs with different sequences were isolated from mouse testis cDNA libraries [6].
• The poly(A) binding protein (PABP), a conserved protein that binds to the 3' poly(A) tail on mRNAs in eukaryotic cells, has been implicated in the regulation of mRNA stability and translation [6].
• The levels of PABP mRNA in testis are 5-10-fold higher than in these somatic tissues, but surprisingly the vast majority of all PABP mRNA size variants sediment more slowly than single ribosomes, indicating strong translational repression [6].
• A single, 70 kDa PABP, whose sequence is highly homologous to vertebrate, yeast and plant PABPs, is detected in oocytes [7].

Associations of Pabpc2 with chemical compounds

• Full RNA-binding potential of PABP in embryo lysates was achieved by brief denaturation with guanidinium hydrochloride followed by dilution for binding and crosslinking or by controlled treatment of lysates with Ca(2+)-dependent micrococcal nuclease [7].

Analytical, diagnostic and therapeutic context of Pabpc2

• Northern blots reveal that there is one major PABP mRNA species in liver, muscle, kidney, and brain, two in spleen, and at least four in testis [6].
• Here, we report studies including UV-crosslinking and immunoblotting assays to characterise PABP in the early developmental stages of the clam Spisula solidissima [7].
• Western blot analysis and immunocytochemistry indicate PABP is widespread in the mammalian testis, with maximal amounts detected in postmeiotic round spermatids [8].

References