Sole and stable RNA duplexes of G-rich sequences located in the 5'-untranslated region of protooncogenes.
Guanine- (G-) rich nucleic acid sequences can form four-stranded structures called G-quadruplexes. It is widely held that the formation of a G-quadruplex in RNA is more feasible than in DNA because of the lack of a complementary strand in mRNA. Here, we analyzed sequences of 5'-untranslated regions of protooncogenes and surprisingly found that these regions showed an enrichment of not only guanine (G) but also cytosine (C) nucleotides. Since neighboring cytosine- (C-) rich regions can affect the formation and stability of a G-quadruplex structure, we further investigated the properties of DNA and RNA structures of G-rich and GC-rich regions. We selected typical GC-rich RNA sequences from protooncogenes and corresponding DNA sequences and investigated their structures. It was found that the GC-rich RNA sequences formed stable A-form duplexes as their major structure independent of the surrounding conditions, including the presence of different cations (Na(+), K(+), or Li(+)) or molecular crowding with 40 wt % poly(ethylene glycol) with an average molecular mass of 200 Da although there are a few exceptions in which only a combination of K(+) and molecular crowding induced a G-quadruplex structure of an extremely G-rich RNA sequence. In contrast, structural polymorphisms involving duplexes, G-quadruplexes, and i-motifs were observed for GC-rich DNA sequences depending on the surrounding factors. These results demonstrate the considerable structural and functional differences in GC-rich sequences of the genome (DNA) and transcriptosome (mRNA) with respect to the nucleic acid backbone. Moreover, it was suggested that structural study for a G-rich RNA sequence should be carried out under cell-mimicking condition where K(+) and crowding cosolutes exist.
Saxena
Sarika
S
Frontier Institute for Biomolecular Engineering Research (FIBER), 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Miyoshi
Daisuke
D
Sugimoto
Naoki
N
D020121:5' Untranslated Regions; D001483:Base Sequence; D003596:Cytosine / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000235:genetics; D054856:G-Quadruplexes; D020862:GC Rich Sequence; D006147:Guanine / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation; D011519:Proto-Oncogenes; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006163:Ribonuclease T1 / Q000378:metabolism; D016415:Sequence Alignment
D020121:5' Untranslated Regions; D006147:Guanine; D012313:RNA; D003596:Cytosine; D004247:DNA; D006163:Ribonuclease T1