Solution structure of an unusually stable RNA tetraplex containing G- and U-quartet structures

Cheong, Chaejoon; Moore, Peter B.

doi:10.1021/bi00151a003

Cited by 272 publications

(224 citation statements)

References 27 publications

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“…The presence of inter-and intramolecular DNA quadruplexes has been described in several instances (13,18,19,20,21) whereas only intermolecular RNA quadruplexes have been reported (22,23). This study suggests that an intramolecular quadruplex is present in the 3'UTR of IGF-ll mRNA.…”

Section: Discussionmentioning

confidence: 57%

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

1994

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Insulin-like growth factor 11 (IGF-ll) 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-11 expression.

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Section: Discussionmentioning

confidence: 57%

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

1994

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“…Structures of guanine-rich tetraplexes have been determined by x-ray crystallography for DNA (20,21) and by NMR for RNA in solution (14). Compared to these models, the G tetraplex region of the present structure has rms deviations of 0.97 Å to the DNA and 1.02 Å to the RNA (NMR).…”

Section: Rna Tetraplex With Sr 2؉ Ions and Other Metal Ionsmentioning

confidence: 88%

“…Despite the biological importance of RNA tetraplexes, their structural basis is not clear yet, and it could be much different from that of DNA tetraplexes. The RNA tetraplex structure UGGGGU was reported by NMR in solution in the presence of monovalent ions (14). To further explore the atomic structure of RNA tetraplexes, we have synthesized, purified, and crystallized the RNA hexamer UGGGGU tetraplex in the presence of divalent Sr 2ϩ ions, and here we report its structure at ultra-high resolution (0.61 Å), which is the highest resolution so far for an RNA.…”

mentioning

confidence: 89%

X-ray analysis of an RNA tetraplex (UGGGGU) ₄ with divalent Sr ²⁺ ions at subatomic resolution (0.61 Å)

Deng

Xiong²,

Sundaralingam³

2001

Proc. Natl. Acad. Sci. U.S.A.

143

106

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Four-stranded guanine tetraplexes in RNA have been identified to be involved in crucial biological functions, such as dimerization of retroviral RNA, translational repression, and mRNA turnover. However, the structural basis for these biological processes is still largely unknown. Here we report the RNA tetraplex structure (UGGGGU) 4 at ultra-high resolution (0.61 Å). The space group is P42 12, and cell constants are a ‫؍‬ b ‫؍‬ 36.16 Å and c ‫؍‬ 74.09 Å. The structure was solved by the multiple-wavelength anomalous dispersion method using a set of three-wavelength data of the isomorphous bromo derivative br UGGGGU and refined to 0.61-Å resolution. Each of the four strands in the asymmetric unit forms a parallel tetraplex with symmetry-related molecules. The tetraplex molecules stack on one another in opposite polarity (headto-head or tail-to-tail) to form a pseudocontinuous column. All of the 5 -end uridines rotate around the backbone of G2, swing out, and form unique octaplexes with the neighboring G tetraplexes, whereas the 3 -end uridines are stacked-in and form uridine tetrads. All of the bases are anti, and the riboses are in the mixed C2 -and C3 -puckering mode. Strontium ions are observed in every other guanine tetrad plane, sitting on the fourfold axis and associated to the eight O6 atoms of neighboring guanine bases in a bipyramidal-antiprism geometry. The hydrogens are clearly observed in the structure. ultra-high resolution ͉ uridine tetrad ͉ octad F or several decades, it has been known that guanine-rich repeats in nucleic acids can form four-stranded tetraplexes in the presence of monovalent ions (1-7) with various biological functions. For example, DNA guanine tetraplexes function in chromosome telomeres (8) and the site-specific recombination of immunoglobulin genes (9). The essential biological functions of RNA tetraplexes have been studied during the past several years. Intramolecular RNA G tetraplex was postulated for a guanine-rich segment adjacent to an endonucleolytic cleavage site in insulin-like growth factor II mRNA (10). Strong evidence has shown that interstrand RNA tetraplexes could be involved in dimerization of HIV 1 genomic RNA, which serves as a critical process in organization of genomic retroviral RNA into infectious virion particles (11). In addition, RNA G tetraplexes have recently been reported to be preferential substrates of bacteriophage fd gene 5 protein (12), which is responsible for the switch from double-stranded to single-stranded viral DNA replication after infection of the bacterial cell. These data indicate that RNA guanine tetraplexes could be crucially involved in translational repression. Furthermore, RNA G tetraplexes have been reported to be specifically targeted by mammalian 5Ј-3Ј exoribonuclease (13), suggesting their potential role in mRNA turnover, which is important in determining the levels and regulation of gene expression. Despite the biological importance of RNA tetraplexes, their structural basis is not clear yet, and it could be much different from ...

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“…G4-RNA has also been studied in detail and shown to form structures based upon G-quartets (Cheong & Moore, 1992). G-RNA can mediate dimerization of the HIV genome in vitro (Marquet et al, 1991;Sundquist & Heaphy, 1993).…”

mentioning

confidence: 99%

A Protein from Tetrahymena thermophila That Specifically Binds Parallel-Stranded G4-DNA

Schierer¹,

Henderson²

1994

Biochemistry

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Solution structure of an unusually stable RNA tetraplex containing G- and U-quartet structures

Cited by 272 publications

References 27 publications

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

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

X-ray analysis of an RNA tetraplex (UGGGGU) ₄ with divalent Sr ²⁺ ions at subatomic resolution (0.61 Å)

A Protein from Tetrahymena thermophila That Specifically Binds Parallel-Stranded G4-DNA

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Solution structure of an unusually stable RNA tetraplex containing G- and U-quartet structures

Cited by 272 publications

References 27 publications

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

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

X-ray analysis of an RNA tetraplex (UGGGGU) 4 with divalent Sr 2+ ions at subatomic resolution (0.61 Å)

A Protein from Tetrahymena thermophila That Specifically Binds Parallel-Stranded G4-DNA

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X-ray analysis of an RNA tetraplex (UGGGGU) ₄ with divalent Sr ²⁺ ions at subatomic resolution (0.61 Å)