A guanosine quadruplex and two stable hairpins flank a major cleavage site in insulin-like growth factor II mRNA

TY - JOUR

T1 - A guanosine quadruplex and two stable hairpins flank a major cleavage site in insulin-like growth factor II mRNA

AU - Christiansen, Jan

AU - Kofod, M

AU - Nielsen, F C

N1 - Keywords: Animals; Base Sequence; Guanine Nucleotides; Humans; Hydrogen Bonding; Hydrolysis; Insulin-Like Growth Factor II; Molecular Sequence Data; Nucleic Acid Conformation; RNA, Messenger; Rats

PY - 1994

Y1 - 1994

N2 - Insulin-like growth factor II (IGF-II) mRNAs are cleaved by an endonucleolytic event in a conserved part of their 3' untranslated region that is predicted to exhibit a complex higher-order RNA structure. In the present study, we have examined the putative secondary structures of in vitro transcripts from the conserved part of human and rat mRNAs by enzymatic and chemical probing. The results show that the cleavage site is situated between two highly structured domains. The upstream domain consists of two large hairpins, whereas the downstream domain is guanosine-rich. The guanosine-rich domain adopts a compact unimolecular conformation in Na+ or K+ but not in Li+, and it completely arrests reverse transcription in K+ but only partially in Na+, indicating the presence of an intramolecular guanosine quadruplex. The flanking higher-order structures may ensure that the cleavage site is not sequestered in stable RNA structures, thus allowing interactions with RNA or proteins at posttranscriptional stages of IGF-II expression.

AB - Insulin-like growth factor II (IGF-II) mRNAs are cleaved by an endonucleolytic event in a conserved part of their 3' untranslated region that is predicted to exhibit a complex higher-order RNA structure. In the present study, we have examined the putative secondary structures of in vitro transcripts from the conserved part of human and rat mRNAs by enzymatic and chemical probing. The results show that the cleavage site is situated between two highly structured domains. The upstream domain consists of two large hairpins, whereas the downstream domain is guanosine-rich. The guanosine-rich domain adopts a compact unimolecular conformation in Na+ or K+ but not in Li+, and it completely arrests reverse transcription in K+ but only partially in Na+, indicating the presence of an intramolecular guanosine quadruplex. The flanking higher-order structures may ensure that the cleavage site is not sequestered in stable RNA structures, thus allowing interactions with RNA or proteins at posttranscriptional stages of IGF-II expression.

M3 - Journal article

C2 - 7838726

SN - 0305-1048

VL - 22

SP - 5709

EP - 5716

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 25

ER -