Introduction of 8-methyladenosine into 2', 5'-oligoadenylate (2-5A) 2'-terminus induces dramatic shift in binding site of RNase L.
The 2',5'-oligoadenylate (2-5A) system is an interferon (IFN)-regulated RNA decay pathway that provides innate immunity against viral infections. The biological action of the 2-5A system is mediated by RNase L, an endoribonuclease that becomes enzymatically active after binding to 2-5A. It has been reported that the 5'-phosphoryl group of 2-5A is required for RNase L activation. However, we have found that 5'-O-dephosphorylated 2-5A tetramer analogs with 8-methyladenosine at the 2'-terminus were more effective as an activator of RNase L than the parent 2-5A (p5'A2'p5'A2'p5'A2'p5'A2'). Introduction of 8-methyladenosine is thought to induce a dramatic shift in the binding site of RNase L.
Nagaoka
Kumi
K
Department of Biomolecular Science, Faculty of Engineering, United Graduate School of Drug Discovery and Medical information Science, Gifu University, Gifu 501-1193, Japan.
Kito
Seiya
S
Kitamura
Yoshiaki
Y
Ueno
Yoshihito
Y
Kitade
Yukio
Y
D000227:Adenine Nucleotides / Q000737:chemistry* / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D001665:Binding Sites; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009843:Oligoribonucleotides / Q000737:chemistry* / Q000378:metabolism
D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; C070330:8-methyladenosine; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D000241:Adenosine