Alternative titles; symbols
HGNC Approved Gene Symbol: PAIP1
Cytogenetic location: 5p12 Genomic coordinates (GRCh38): 5:43,526,267-43,557,411 (from NCBI)
In initiation of translation in eukaryotes, binding of the small ribosomal subunit to mRNA requires recognition of the 5-prime cap structure by the cap-binding complex eIF4F. eIF4F consists of eIF4E (133440), eIF4A (see 602641), and eIF4G (see 600495). Translation initiation is further regulated by the mRNA 3-prime poly(A) tail and the poly(A)-binding protein (PABC1; 604679). PAIP1 interacts with PABC1 and some eIF4 complexes.
By Far Western blot analysis of HeLa cell extracts and a placenta cDNA library using a PABC1 probe, Craig et al. (1998) identified a cDNA encoding PAIP1 (PABC1-interacting protein-1). Sequence analysis of the deduced 480-amino acid PAIP1 protein predicted that it shares 39% amino acid similarity with the central portion of eIF4G, which contains an eIF4A-binding region. PAIP1 also contains a proline-rich N terminus. SDS-PAGE analysis determined that PAIP1 is expressed as a 70-kD protein.
Binding analysis by Craig et al. (1998) showed that PAIP1 binds strongly to poly(A) only in the presence of PABC1. Immunoprecipitation and Western blot analysis demonstrated that in HeLa extracts, the C terminus of PAIP1 interacts with PABC1, and PAIP1 interacts with eIF4A but not eIF4G complexes.
AU-rich elements and protein-coding determinants direct rapid removal of poly(A) tails as a necessary first step in mRNA decay. Grosset et al. (2000) determined that 5 proteins form a multiprotein complex associated with the major protein-coding-region determinant of instability (mCRD) of the FOS gene (164810): PABP, HNRNPD (601324), PAIP1, NSAP1, and UNR (191510). Overexpression of these proteins stabilized mCRD-containing mRNA by impeding deadenylation.
Craig, A. W. B., Haghighat, A., Yu, A. T. K., Sonenberg, N. Interaction of polyadenylate-binding protein with the eIF4G homologue PAIP enhances translation. Nature 392: 520-523, 1998. [PubMed: 9548260] [Full Text: https://doi.org/10.1038/33198]
Grosset, C., Chen, C.-Y. A., Xu, N., Sonenberg, N., Jacquemin-Sablon, H., Shyu, A.-B. A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex. Cell 103: 29-40, 2000. [PubMed: 11051545] [Full Text: https://doi.org/10.1016/s0092-8674(00)00102-1]