hnRNP K binds a core polypyrimidine element in the eukaryotic translation initiation factor 4E (eIF4E) promoter, and its regulation of eIF4E contributes to neoplastic transformation - PubMed (original) (raw)

Polypyrimidine elements in mammalian translation initiation factor promoters. The genomic sequences of thirty-eight human translation initiation factor genes (eIFs) were identified by using LocusLink (104). Five thousand nucleotides 5′ to and 3′ to the transcription initiation site of each gene were downloaded into Clone Manager Suite 7 for further manipulation (Scientific and Educational Software, Durham, N.C.). The immediate promoter regions of all of these sequences were inspected for sequences containing stretches of eight or more pyrimidines that were less than 20 nucleotides from the transcription initiation site or the translation initiation codon. Thirteen human eIFs revealed such sequences. Two thousand nucleotides surrounding the transcription initiation site of the 13 candidates were then used in a BLAST search of the mouse and rat genomes. Promoter regions were considered to be confirmed if this region showed >70% homology, and it fell within a calculated CpG island in all three species. The polypyrimidine stretches were conserved between mouse, rat, and human genomes in nine of the confirmed promoter candidates as shown. Listed are the 70 nucleotides containing the proximal promoter sequences from all three species for the nine candidates containing conserved polypyrimidine stretches, and the polypyrimidine stretches are identified by gray highlighting. The transcription initiation sites identified in the genome databases were confirmed or modified by a BLAST comparison of each genomic sequence against available expressed sequence tag sequences for each species. Indicated as white letters against a black background are either the site listed in LocusLink as the transcription initiation site, the site mapping of the 5′ end of the majority of all of the available ests for the indicated species, or the 5′-most expressed sequence tag sequence if no consensus 5′ end was obvious. The translation initiation codon (ATG) is identified for the eight candidates where it is positioned close to the transcription initiation site. Myc binding sites (

CACGTG

) were identified by locating Pm1I sites in each promoter and are shown in boldface, underlined italics with gray highlighting. Remarkably, Myc binding sites were located at extremely short distances from the initiation site of seven of the nine candidate promoters; four were within 50 nucleotides, two were at about 150 nucleotides, and one was about 500 nucleotides distant. A nuclear respiratory factor 1α palindromic sequence (NRF-1=α PAL) binding site that also binds max and may be an alternative Myc binding site is identified in the eIF2S2 promoters. LocusLink identifications include eIF2S2 (human 8894, mouse 67204, and rat 296302), eIF2S3 (1968, 26905, and 299027), eIF3S1 (8669, 78655, and 311371), eIF3S3 (8667, 68135, and 299899), eIF3S5 (8665, 66085, and 293427), eIF3S6 (3646, 16341, and 299872), eIF3S10 (8661, 75705, and 300253), eIF4B (1975, 75705, and 300253), and eIF4E (1977, 13684, and 117045). The eIF3S1 mouse promoter sequences are assumed based on their homology to the rat and human sequences. We found no mouse cDNA or EST sequence that matched this sequence, and it was not annotated as the promoter sequence in the genome database.