Crystallization of oligonucleotides containing A-rich repeats suggests a structural contribution to the autoregulation mechanism of PABP translation.
Eukaryotic poly(A)-binding protein (PABP) commonly binds to the 3'-UTR poly(A) tail of every mRNA, but it also binds to the 5'-UTR of PABP mRNA for autoregulation of its expression. In the sequence of the latter binding site, the contiguous A residues are segmented discretely by the insertion of short pyrimidine oligonucleotides as linkers, so that (A)(6-8) segments are repeated six times. This differs from the poly(A)-tail sequence, which has a higher binding affinity for PABP. In order to examine whether the A-rich repeats have a functional structure, several RNA/DNA analogues were subjected to crystallization. It was found that some of them could be crystallized. Single crystals thus obtained diffracted to 4.1 Å resolution. The fact that the repeated sequences can be crystallized suggests the possibility that the autoregulatory sequence in PABP mRNA has a specific structure which impedes the binding of PABP. When PABP is excessively produced, it could bind to this sequence by releasing the structure in order to interfere with initiation-complex formation for suppression of PABP translation. Otherwise, PABP at low concentration preferentially binds to the poly(A) tail of PABP mRNA.
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuda, Midori-ku, Yokohama, Japan.
Keita
K
Kikuchi
Satoru
S
Shimizu
Yoshiteru
Y
Sato
Ella Czarina
EC
Morishita
Akio
A
Takénaka
D003460:Crystallization; D011061:Poly A / Q000737:chemistry*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D011131:Polyribonucleotides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D012091:Repetitive Sequences, Nucleic Acid
D039102:Poly(A)-Binding Proteins; D011131:Polyribonucleotides; D011061:Poly A